Modified Karhunen-Loéve expansion for evaluating skin-colour-associated melanoma risk factors

An approach based on the modified Karhunen-Loéve expansion (MKLE) of constitutive and facultative skin colour data acquired by colorimeters in melanoma patients and healthy control subjects, was used to identify two colour features defining skin-colour-associated risk of melanoma. None of four common statistical classifiers trained on colour features were sufficiently accurate for allowing skin colour alone to be used for classification purposes, though a Bayesian quadratic classifier matched the transformed data well. This study supersedes the indeterminate character of most common clinical criteria based on qualitative factors and, irrespective of the results of classification, provides objective skin colour information for the prevention of melanoma.     

"Constitutive" skin pigmentation: a marker of breast cancer risk?

There is much evidence to support a link between oestrogen and breast cancer. Both adult and foetal oestrogen may have this predisposing effect, and between-individual and between-population differences in oestrogen may account for much of the variation in risk for breast cancer. Here we suggest that "constitutive" skin colour in women is a marker for prenatal and adult oestrogen levels such that within ethnic groups light-skinned women have experienced higher in utero and adult oestrogen than dark-skinned women. Scores for 'constitutive' skin pigment may therefore be predictive of risk for breast cancer and low scores could be used to identify individuals at high risk.     

Lesion area assessment in psoriasis patients

Psoriasis is an autoimmune skin disease, afflicting skin with red plaques that are usually accompanied by silvery-white scales. Various medical treatments are used, with different impacts on the patients, but there is no definite cure for the disease. The PASI standard is employed to measure the performance of the treatments. It includes four parameters, namely area, erythema, scaliness and skin thickness. The PASI parameters are usually measured manually by physicians through subjective clinical observations which are imprecise, time consuming and in some cases lead to diverse results. This paper presents a computer-based automatic method to measure the area parameter in the PASI standard. In the proposed method, the YCbCr colour space is used to differentiate the plaques from the skin by applying an optimal threshold method. Performance evaluation results indicate that the proposed method is able to determine lesion areas with accuracy higher than 96% for 18 out of 20 cases and higher than 92% for another case. As well as high accuracy the proposed method has another advantage over previous methods: it can automatically detect plaques with silvery-white scales, plaques on hairy skins and tiny plaques, as well as simple (scale-less) plaques.     

Colour in digital pathology: a review

Colour is central to the practice of pathology because of the use of coloured histochemical and immunohistochemical stains to visualize tissue features. Our reliance upon histochemical stains and light microscopy has evolved alongside a wide variation in slide colour, with little investigation into the implications of colour variation. However, the introduction of the digital microscope and whole‐slide imaging has highlighted the need for further understanding and control of colour. This is because the digitization process itself introduces further colour variation which may affect diagnosis, and image analysis algorithms often use colour or intensity measures to detect or measure tissue features. The US Food and Drug Administration have released recent guidance stating the need to develop a method of controlling colour reproduction throughout the digitization process in whole‐slide imaging for primary diagnostic use. This comprehensive review introduces applied basic colour physics and colour interpretation by the human visual system, before discussing the importance of colour in pathology. The process of colour calibration and its application to pathology are also included, as well as a summary of the current guidelines and recommendations regarding colour in digital pathology.     

Remote sensing of physiological signs using a machine vision system

The aim of this work is to remotely measure heart rate (HR) and respiratory rate (RR) using a video camera from long range (>?50 m). The proposed system is based on imperceptible signals produced from blood circulation, including skin colour variations and head motion. As these signals are not visible to the naked eye and to preserve the signal strength in the video, we used an improved video magnification technique to enhance these invisible signals and detect the physiological activity within the subject. The software of the proposed system was built in a graphic user interface (GUI) environment to easily select a magnification system to use (colour or motion magnification) and measure the physiological signs independently. The measurements were performed on a set of 10 healthy subjects equipped with a finger pulse oximeter and respiratory belt transducer that were used as reference methods. The experimental results were statistically analysed by using the Bland–Altman method, Pearson's correlation coefficient, Spearman correlation coefficient, mean absolute error, and root mean squared error. The proposed system achieved high correlation even in the presence of movement artefacts, different skin tones, lighting conditions and distance from the camera. With acceptable performance and low computational complexity, the proposed system is a suitable candidate for homecare applications, security applications and mobile health devices.     

Sexual selection as a cause of human skin colour variation: Darwin's hypothesis revisited

The dark skin of tropical peoples is likely to be an adaptation to the strong ultraviolet (UV) radiation near the equator, perhaps protecting against sunburn or degradation of folate. By contrast, the adaptive value of light skin is questionable. In particular, the relevance of vitamin D deficiency rickets as a selective factor has been cogently criticized. Population genetic studies on the melanocortin 1 receptor (MC1R) gene (one of the genes responsible for normal human skin colour variation) also cast doubt on the role of positive natural selection in the evolution of light skin. Natural selection may favour dark skin everywhere, though to a lesser extent at higher latitudes. Darwin believed that racial differences in skin colour were caused by sexual selection. Available evidence suggests that in each society a lighter-than-average skin colour is preferred in a sexual partner. Such a preference would generate sexual selection for light skin that counteracts natural selection for dark skin. The observed latitudinal gradient in skin colour may result from the balance between natural and sexual selection.     

Sexual selection as a cause of human skin colour variation: Darwin's hypothesis revisited

The dark skin of tropical peoples is likely to be an adaptation to the strong ultraviolet (UV) radiation near the equator, perhaps protecting against sunburn or degradation of folate. By contrast, the adaptive value of light skin is questionable. In particular, the relevance of vitamin D deficiency rickets as a selective factor has been cogently criticized. Population genetic studies on the melanocortin 1 receptor (MC1R) gene (one of the genes responsible for normal human skin colour variation) also cast doubt on the role of positive natural selection in the evolution of light skin. Natural selection may favour dark skin everywhere, though to a lesser extent at higher latitudes. Darwin believed that racial differences in skin colour were caused by sexual selection. Available evidence suggests that in each society a lighter-than-average skin colour is preferred in a sexual partner. Such a preference would generate sexual selection for light skin that counteracts natural selection for dark skin. The observed latitudinal gradient in skin colour may result from the balance between natural and sexual selection.     

Colour-spatial vision

A critical survey is made of neurophysiological and psychophysiological investigations of colour vision. A neuronal model of colour-spatial vision is suggested. The model allows a unified explanation of the whole range of psychophysiological phenomena: the mixing of colours of high-frequency image components, the McCollough type colour after-effects, the simultaneous and successive colour contrast, the hue constancy perception, the appearance of non-spectral colours by mixing of monochromatic lights. A suggestion is made as to the existence of two main mechanisms of colour vision. The first of these, by means of Fourier transforms, gives a set of coefficients which describes the spatial distribution of light (quantity of energy) and hue (quality of energy) in the visual field. The second mechanism establishes colour names in each chromatically homogenous area of the field described by the first mechanism. Both mechanisms cooperate on the basis of their common spatial organization.     

A skin colour code for the Nigerian (Negroid) population

Some researchers have codified various people of different racial and pigment backgrounds into skin types. The West African native population generally falls into type VI--least likely to burn. There is a need for skin colour code in a multiethnic country like Nigeria especially for the purpose of health matters. The human eye is still the most accurate instrument for the measurement of colour; its interpretation however is subjective. An objective form of documentation is needed that will be simple, quick and inexpensive. To meet the challenge for the development of a skin colour code for Nigerians, a study was conducted at the University College Hospital (UCH) Ibadan, Nigeria. The study aimed at visually identifying possible skin colours and to reproduce this on the computer. 40 colour chips were identified and found relevant for the Negroid skin in Nigeria including the Nigerian albino. The chart can be laminated using thin transparent plastic film to prevent transmission of infection from skin to skin in different people. A skin colour code can be useful for clinical evaluation of disease conditions like vitiligo as well as for epidemiological studies. Its diagnostic potential is yet to be assessed.     

Risk factors in Central Poland for the development of superficial and nodular basal cell carcinomas

Introduction

In the last decades the number of skin carcinomas has dramatically increased, which is mainly connected with changes in lifestyle, especially with common use of artificial light sources such as sunbeds. Basal cell carcinoma (BCC) is the most common form of skin cancer in white populations. Basal cell carcinomas are divided into subtypes, depending on their clinical picture and histology. The main groups are nodular (nBCC) and superficial (sBCC) ones. The major recognized risk factors for basal cell carcinoma (BCC) are exposure to chronic and intermittent burning doses of sunlight. Other risk factors leading to the development of the nBCC and sBCC subtypes of BCC are not well established.

Material and methods

An analysis of 123 patients with either nBCC or sBCC, living in Lodz, Poland, regarding various intrinsic and environmental parameters was undertaken following the histological diagnosis of BCC.

Results

No statistical differences were observed between the BCC subtype and sex, age, hair colour, eye colour, smoking, family history of skin cancer, occupation, or past episodes of sunburn. While sBCCs tended to occur on unexposed body sites in phototype I/II subjects who mainly avoided direct sunlight, nBCCs tended to occur on sun-exposed body sites in phototype III subjects who were frequently in direct sunlight.

Conclusions

Thus the development of particular BCC subtypes is partially dependent on phototype and personal sun behaviour.     

Colour stability and visual perception of dimethacrylate based dental composite resins

The spectrophotometric method of colour measurement was applied to an investigation of the colour stability of dimethacrylate based composite resins exposed to thermal and photochemical aging. A good correlation was observed between visual perception of colour change and the spectrophotometric colour difference [delta E (FMC-2)] of unexposed and aged specimens, but 50% of the observers considered the colour match of two specimens to be clinically unacceptable when the colour difference exceeded 10.6. Kinetic studies of thermally and photochemically induced colour change showed a sigmoidal dependence of colour change on the logarithm of exposure time. Because the direction and magnitude of the colour change differed for the two procedures, it would appear that different mechanisms are involved.     

Signatures of Positive Selection in Genes Associated with Human Skin Pigmentation as Revealed from Analyses of Single Nucleotide Polymorphisms

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway ( SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD ) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans ( OCA2, TYRP1 and KITLG ) and in Asians ( OCA2, DCT, KITLG, EGFR and DRD2 ), whereas signals were scarce in Africans ( DCT, EGFR and DRD2 ). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.     

Association of Polymorphic Sites in the OCA2 Gene with Eye Colour Using the Tree Scanning Method

A number of genes are considered to affect normal variation in human pigmentation. Recent studies have indicated that OCA2 is the crucial gene involved in the high variation of iris colour present among populations of European descent. In this study, eleven polymorphisms of the OCA2 gene were examined in search of their association with different pigment traits. The evolutionary tree scanning method indicated that the strongest phenotypic eye colour variation is associated with the branch defined by nonsynonymous change rs1800407, which refers to amino acid causing change Arg419Gln located in exon 13. Single SNP analysis indicated that allele 419Gln is associated with green/hazel iris colour (p < 0.001). According to tree scanning analysis, the proportion of eye colour variation explained by this nucleotide position is merely 4%. Thus, additional variation present in the OCA2 gene and perhaps some other pigment related genes must be taken into account in order to explain the high phenotypic variation in iris colour.     

Postmortem changes in skin color

By the employment of the colorimetric method statistically significant objective data on postmortem changes in the colour of different parts of the skin have first been obtained. Histological and spectrophotometric studies were carried out in order to elucidate the causes of these changes. The colour of the cadavar skin as well as the colour of the human skin in life depends on primary pigments: hemoglobin, melanin, carotene and melanoid. A certain role is likely to be played by the main structural proteins of the derma and epidermis: collagen and keratin. The cadavar skin colour differs in variations of the dominant wave length and reflectance which are associated with postmortem redistribution of the blood under the effect of the gravity and qualitative transformation of oxyhaemoglobin into reduced haemoglobin. The distribution of melanin, carotene, and melanoid does not differ from that in life. The most specific index of the amount of melanin is the purity of colour and not reflectance.     

Colour and brightness signals of parvocellular lateral geniculate neurons

Summary We recorded from single neurons in the parvocellular layers of the lateral geniculate body of anesthetized monkeys. Spectral response curves of parvocellular neurons depended on the luminance ratio between the chromatic stimuli and achromatic background. From response/intensity curves, we determined the relative luminance between a coloured and an achromatic (white) light at which a given cell became non-responsive (critical luminance ratio, CLR). The spectral dependence of the CLRs of narrow (N) and wide band (W) cells with opponent receptor input showed characteristic differences. The activity of W-cells increased with luminance increase of a white light and of a coloured light in the specific spectral region of the cell (yellow-red for the long wave length sensitive WL-, and yellow-green-blue for the short wave length sensitive WS-cells), while N-cells were activated by their specific spectral light (blue for NS-cells, red for NL-cells) and by a luminance decrease of achromatic white. N-cells discriminate best between their characteristic colour and white at luminance ratios below their respective CLR, while W-cells distinguish best between a light of their characteristic colour and white at chromatic/ achromatic luminance ratios above their respective CLR. Yellow sensitive W-cells with a narrow spectral sensitivity peaking around 570 nm and with only a small or no response to white light, could enable distinction between white and yellow of similar luminance. The findings are consistent with the opponency model of spectrally sensitive cells in the LGB. We discuss their implications for colour coding by parvocellular cells. N- and W-cells appear to behave complementary with respect to luminance information (N-cells may be compared to the cat's off-cells, W-cells to on-cells). S- and L-cells are complementary with respect to colour. The yellow sensitive WM-cells are critical for the discrimination of yellow and white, while cells with excitatory cone input from blue and red cones (W-SL-cells) may aid the perception of purple. The fact that, at different relative luminance ratios between a chromatic stimulus and a white background, the whole family of parvocellular cells is involved differently in coding for colour, may explain the different appearance of colours against a white background at different luminance ratios and the perception of induced colours.This work was supported by a NATO collaborative research grant to Dr. Arne Valberg (650/83)     

Objective assessment of psoriasis erythema for PASI scoring

Skin colour is vital information in dermatological diagnosis as it reflects the pathological condition beneath the skin. It is commonly used to indicate the extent of diseases such as psoriasis, which is indicated by the appearance of red plaques. Although there is no cure for psoriasis, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, the current gold standard method, PASI (Psoriasis Area and Severity Index), is used to determine severity of psoriasis lesion. Erythema (redness) is one parameter in PASI and this condition is assessed visually, thus leading to subjective and inconsistent results. Current methods or instruments that assess erythema have limitations, such as being able to measure erythema well for low pigmented skin (fair skin) but not for highly pigmented skin (dark skin) or vice versa. In this work, we proposed an objective assessment of psoriasis erythema for PASI scoring for different (low to highly pigmented) skin types. The colour of psoriasis lesions are initially obtained by using a chromameter giving the values L*, a*, and b* of CIELAB colour space. The L* value is used to classify skin into three categories: low, medium and highly pigmented skin. The lightness difference (ΔL*), hue difference (Δh_ab), chroma (ΔC*_ab) between lesions and the surrounding normal skin are calculated and analysed. It is found that the erythema score of a lesion can be distinguished by their Δh_ab value within a particular skin type group. References of lesion with different scores are obtained from the selected lesions by two dermatologists. Results based on 38 lesions from 22 patients with various level of skin pigmentation show that PASI erythema score for different skin types i.e. low (fair skin) to highly pigmented (dark skin) skin types can be determined objectively and consistent with dermatology scoring.     

Surgery: Colour Doppler ultrasound guidance for transcervical wire tuboplasty

To evaluate the usefulness of high-resolution ultrasound withcolour Doppler mapping system in performing transcervical wiretuboplasty, 13 infertile women with bilateral proximal tubalobstruction demonstrated by X-ray or colour Doppler ultrasoundhysterosalpingography and chromoperturbation at laparoscopywere treated by transcervical wire tuboplasty utilizing colourDoppler mapping ultrasound guidance. A co-axial catheter wasused to introduce a 0.016-in. flexible wire to the occludedportion. Transcervical wire catheterization was accomplishedin 25 of 26 tubes (96%), resulting in patency in 24 of 25 tubes(96%). At the end of the procedure all patients had at leastone tube patent (100%). Five (38%) women achieved pregnancieswithin 1 year after the procedure. High-resolution ultrasoundwith colour Doppler mapping system is an efficacious way toperform transcervical wire tuboplasty, avoiding the risk ofradiation and allergic reaction.     

Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin

Methylated lysine 27 on histone H3 (H3K27me) marks repressed “facultative heterochromatin,” including developmentally regulated genes in plants and animals. The mechanisms responsible for localization of H3K27me are largely unknown, perhaps in part because of the complexity of epigenetic regulatory networks. We used a relatively simple model organism bearing both facultative and constitutive heterochromatin, Neurospora crassa, to explore possible interactions between elements of heterochromatin. In higher eukaryotes, reductions of H3K9me3 and DNA methylation in constitutive heterochromatin have been variously reported to cause redistribution of H3K27me3. In Neurospora, we found that elimination of any member of the DCDC H3K9 methylation complex caused massive changes in the distribution of H3K27me; regions of facultative heterochromatin lost H3K27me3, while regions that are normally marked by H3K9me3 became methylated at H3K27. Elimination of DNA methylation had no obvious effect on the distribution of H3K27me. Elimination of HP1, which “reads” H3K9me3, also caused major changes in the distribution of H3K27me, indicating that HP1 is important for normal localization of facultative heterochromatin. Because loss of HP1 caused redistribution of H3K27me2/3, but not H3K9me3, these normally nonoverlapping marks became superimposed. Indeed, mass spectrometry revealed substantial cohabitation of H3K9me3 and H3K27me2 on H3 molecules from an hpo strain. Loss of H3K27me machinery (e.g., the methyltransferase SET-7) did not impact constitutive heterochromatin but partially rescued the slow growth of the DCDC mutants, suggesting that the poor growth of these mutants is partly attributable to ectopic H3K27me. Altogether, our findings with Neurospora clarify interactions of facultative and constitutive heterochromatin in eukaryotes.It has become increasingly clear that covalent modifications of chromatin, such as methylation of specific histone residues and methylation of DNA, can have profound effects on genome functions. In animals, even partial disruption of DNA methylation leads to developmental defects and disease states (Robertson 2005). Similarly, methylation of histone H3 lysine 27 (H3K27me) by the Polycomb Repressive Complex 2 (PRC2) is critical for normal development in flies, plants, and other systems (Schwartz and Pirrotta 2007), and recent work implicates perturbation of H3K27me in a high fraction of pediatric gliomas (Schwartzentruber et al. 2012; Sturm et al. 2012; Wu et al. 2012; Chan et al. 2013; Lewis et al. 2013). It is of obvious interest to understand the normal regulation of epigenetic features such as methylation of DNA and H3K27, which normally mark constitutive and facultative heterochromatin, respectively. Unfortunately, despite numerous studies in a variety of systems, little is understood about how these chromatin modifications are controlled.Epigenetic marks frequently influence one another, confounding analyses. For example, Schmitges et al. (2011) demonstrated that the amino terminus of histone H3 is recognized by the Nurf55-Suz12 submodule of PRC2 and that this binding is blocked by marks of active chromatin, namely, K4me3 and K36me2/3. Although the mechanism of such “crosstalk” is sometimes reasonably obvious, more often it is not, as illustrated by observations of H3K27me3 redistribution in response to defects in constitutive heterochromatin. More than a decade ago, Peters et al. (2003) noticed that mouse cells defective in both of the SUV39H methyltransferases, which are responsible for the trimethylation of histone H3 lysine 9 (H3K9me3) characteristic of pericentric heterochromatin, show redistribution of H3K27me3; both cytological and molecular analyses suggested that this Polycomb mark “relocated” to the neighborhood abandoned by H3K9me3. DNA methylation typically colocalizes with H3K9me3 but not with H3K27me3 (Rose and Klose 2014). Because DNA methylation can depend on H3K9me, and vice versa (Tariq and Paszkowski 2004), it was of interest to determine whether loss of DNA methylation would also result in redistribution of H3K27me. In early studies with mouse embryonic stem cells, reduced DNA methylation resulting from mutation of either the maintenance methyltransferase gene dnmt1 or the de novo DNA methyltransferase genes dmnt3a and dnmt3b did not result in an obvious change in the distribution of H3K27me (Martens et al. 2005). However, subsequent studies with Arabidopsis (Mathieu et al. 2005; Deleris et al. 2012), mouse embryonic fibroblasts (Lindroth et al. 2008; Reddington et al. 2013), embryonic stem cells (Hagarman et al. 2013), and neural stem cells (Wu et al. 2010) revealed that loss of DNA methylation, caused by disruption of DNA methyltransferase genes or treatment with the demethylating agent 5-azacytidine, provided the most potent trigger of H3K27me3 redistribution.Considering that DNA methylation has been reported to stimulate H3K9 methylation, in both plants (Tariq and Paszkowski 2004) and animals (Jin et al. 2011), and that both of these epigenetic marks are tied to additional nuclear processes, interpretation of these fascinating results is problematic. We took advantage of a relatively simple system to explore possible relationships between marks of constitutive and facultative heterochromatin. Specifically, we used the filamentous fungus Neurospora crassa, which unlike many other simple model eukaryotes (e.g., budding and fission yeasts, Drosophila and Caenorhabditis elegans) has both DNA methylation and H3K27me (Aramayo and Selker 2013; Jamieson et al. 2013). The pathway for formation of constitutive heterochromatin in Neurospora is relatively well understood and essentially unidirectional, as illustrated in Figure 1A. Constitutive heterochromatin, which is primarily in centromere regions, is characterized by AT-rich (GC-poor) DNA resulting from the action of the genome defense system RIP (repeat-induced point mutation) operating on transposable elements (Selker 1990; Aramayo and Selker 2013). DIM-5, in the DIM-5/DIM-7/DIM-9/DDB1/CUL4 complex (DCDC) (Fig. 1B), methylates H3K9 associated with RIP''d DNA (Lewis et al. 2010a,b). Heterochromatin Protein 1 (HP1) specifically binds the resulting H3K9me3 (Freitag et al. 2004) and recruits the DNA methyltransferase DIM-2 (Honda and Selker 2008). Consequently, the genomic distribution of 5mC, HP1, H3K9me3, AT-rich DNA, and repeated sequences correlate almost perfectly (Fig. 1A). Importantly, mutation of dim-2 does not affect the distributions of H3K9me3 and HP1, unlike the situation in plants (Tariq and Paszkowski 2004) and animals (Espada et al. 2004; Gilbert et al. 2007). Similarly, mutation of the gene encoding HP1 (hpo) has almost no effect on the distribution of H3K9me3 (Lewis et al. 2009). Although mutations in genes encoding DCDC proteins render the organism slow-growing and sensitive to certain drugs (Lewis et al. 2010a), neither the components of the DNA methylation/constitutive heterochromatin machinery nor the components of the H3K27me2/3/facultative heterochromatin machinery are essential for viability of the organism, allowing us to test knockouts of genes for components of these processes for possible epigenetic interactions.Open in a separate windowFigure 1.Heterochromatin formation in Neurospora crassa. (A) An ∼500-kb region, including the centromere of LG III, is shown to illustrate the pathway leading to constitutive heterochromatin in Neurospora. During the sexual phase of the life cycle, the genome defense system RIP (repeat-induced point mutation) recognizes repeated DNA (e.g., transposons and other repeated DNA shown as black rectangles) and litters them with C:G-to-T:A mutations (Selker 1990). In vegetative cells, lysine 9 of histone H3 (H3K9) associated with G:C-poor DNA is methylated by DIM-5, generating H3K9me3 (orange track), which is bound by the HP1-DIM-2 complex (yellow track) and catalyzes DNA methylation (green track). Perturbation of any step in the pathway eliminates the downstream steps without significantly influencing earlier steps. (B) Key proteins required to form constitutive (left) or facultative (right) heterochromatin. Methylation of H3K9 by DIM-5 depends on all five members of the DCDC (DIM-5/-7/-9, CUL4/DDB1 complex) (Lewis et al. 2010a). HP1 directly binds to H3K9me3 (cluster of three red hexagons labeled “Me”) and recruits the DNA methyltransferase DIM-2 (Honda and Selker 2008), resulting in a genome-wide correlation between H3K9me3 and DNA methylation (orange hexagons labeled “Me”) (Lewis et al. 2009). HP1 is also involved in the HCHC deacetylase silencing complex (Honda et al. 2012) and the DMM (Honda et al. 2010) complex, which limits spreading of constitutive heterochromatin. Methylation of H3K27 (cluster of three blue hexagons labeled “Me”) is carried out by the PRC2 complex consisting of SET-7, EED, SU(Z)12, and NPF (Jamieson et al. 2013).