title: 3D chromatin interactions organize Yan chromatin occupancy and repression at the even-skipped locus.
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.
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA;
authors.forename: Jemma L
authors.initials: JL
authors.lastname: Webber
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Aaron
authors.initials: A
authors.lastname: Mitchell-Dick
authors.forename: Ilaria
authors.initials: I
authors.lastname: Rebay
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C076188:AOP protein, Drosophila; D002843:Chromatin; D029721:Drosophila Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C052837:eve protein, Drosophila
keywords: Drosophila; ETS transcription factor; chromatin conformation; gene regulation; heart development; robustness