Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg.     

CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells

BTLA (B- and T-lymphocyte attenuator) is a prominent co-receptor that is structurally and functionally related to CTLA-4 and PD-1. In T cells, BTLA inhibits TCR-mediated activation. In B cells, roles and functions of BTLA are still poorly understood and have never been studied in the context of B cells activated by CpG via TLR9. In this study, we evaluated the expression of BTLA depending on activation and differentiation of human B cell subsets in peripheral blood and lymph nodes. Stimulation with CpG upregulated BTLA, but not its ligand: herpes virus entry mediator (HVEM), on B cells in vitro and sustained its expression in vivo in melanoma patients after vaccination. Upon ligation with HVEM, BTLA inhibited CpG-mediated B cell functions (proliferation, cytokine production, and upregulation of co-stimulatory molecules), which was reversed by blocking BTLA/HVEM interactions. Interestingly, chemokine secretion (IL-8 and MIP1β) was not affected by BTLA/HVEM ligation, suggesting that BTLA-mediated inhibition is selective for some but not all B cell functions. We conclude that BTLA is an important immune checkpoint for B cells, as similarly known for T cells.     

Assessment of family history of colorectal cancer in primary care: Perceptions of first degree relatives of people with colorectal cancer

Objective

First degree relatives (FDRs) of someone with colorectal cancer (CRC) are at increased risk of the disease. In this study we examine the factors associated with discussing family history of CRC with a health professional.

Methods

People with CRC, recruited through the population-based Victorian Cancer Registry in Australia, were asked to refer FDRs to the study. Eight hundred and nineteen FDRs completed a telephone interview.

Results

Thirty-six percent of FDRs recalled ever being asked about their family history of bowel cancer by a health professional. Factors associated with having this discussion were being aged 50–60 years, having a university education, being in the potentially high risk category, being very worried about getting bowel cancer and knowing that family history increases risk through discussions with family, friends or their own education.

Conclusion

Despite evidence that doctor endorsement is a key factor in the uptake of CRC screening, our study shows that the majority of FDRs do not recall being asked by a health professional about their family history.

Practice implications

There is a need to identify the most appropriate method to improve rates of health professional discussion of family history with relatives of CRC patients in order to improve screening rates.