3D chromatin interactions organize Yan chromatin occupancy and repression at the even-skipped locus |
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Authors: | Jemma L. Webber Jie Zhang Aaron Mitchell-Dick Ilaria Rebay |
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Affiliation: | 1.Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA;;2.Committee on Cancer Biology, University of Chicago, Chicago, Illinois 60637, USA |
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Abstract: | Long-range integration of transcriptional inputs is critical for gene expression, yet the mechanisms remain poorly understood. We investigated the molecular determinants that confer fidelity to expression of the heart identity gene even-skipped (eve). Targeted deletion of regions bound by the repressor Yan defined two novel enhancers that contribute repressive inputs to stabilize tissue-specific output from a third enhancer. Deletion of any individual enhancer reduced Yan occupancy at the other elements, impacting eve expression, cell fate specification, and cardiac function. These long-range interactions may be stabilized by three-dimensional chromatin contacts that we detected between the elements. Our work provides a new paradigm for chromatin-level integration of general repressive inputs with specific patterning information to achieve robust gene expression. |
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Keywords: | Drosophila ETS transcription factor chromatin conformation gene regulation heart development robustness |
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