title: An Organizational Hub of Developmentally Regulated Chromatin Loops in the Drosophila Antennapedia Complex.
abstract: Chromatin boundary elements (CBEs) are widely distributed in the genome and mediate formation of chromatin loops, but their roles in gene regulation remain poorly understood. The complex expression pattern of the Drosophila homeotic gene Sex combs reduced (Scr) is directed by an unusually long regulatory sequence harboring diverse cis elements and an intervening neighbor gene fushi tarazu (ftz). Here we report the presence of a multitude of CBEs in the Scr regulatory region. Selective and dynamic pairing among these CBEs mediates developmentally regulated chromatin loops. In particular, the SF1 boundary plays a central role in organizing two subsets of chromatin loops: one subset encloses ftz, limiting its access by the surrounding Scr enhancers and compartmentalizing distinct histone modifications, and the other subset subdivides the Scr regulatory sequences into independent enhancer access domains. We show that these CBEs exhibit diverse enhancer-blocking activities that vary in strength and tissue distribution. Tandem pairing of SF1 and SF2, two strong CBEs that flank the ftz domain, allows the distal enhancers to bypass their block in transgenic Drosophila, providing a mechanism for the endogenous Scr enhancer to circumvent the ftz domain. Our study demonstrates how an endogenous CBE network, centrally orchestrated by SF1, could remodel the genomic environment to facilitate gene regulation during development.
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.
authors.forename: Jiayang K
authors.initials: JK
authors.lastname: Liu
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.
authors.forename: Sapna K
authors.initials: SK
authors.lastname: Patel
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.
authors.forename: Derrick C
authors.initials: DC
authors.lastname: Lane
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, USA hcai@uga.edu.
authors.forename: Haini N
authors.initials: HN
authors.lastname: Cai
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051943:Antennapedia Homeodomain Protein / Q000235:genetics*; D002843:Chromatin / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D051717:Fushi Tarazu Transcription Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D038101:Insulator Elements; D011401:Promoter Regions, Genetic; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C491517:SF1 protein, Drosophila; C519409:SF2 protein, Drosophila; C059627:Scr protein, Drosophila; D014157:Transcription Factors; C497169:ftz protein, Drosophila