title: Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture.
abstract: Eukaryotic gene expression is regulated by enhancer-promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer-promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions. hkCP enhancers contain H3K4me3 and exclusively bind Cap-H2, Chromator, DREF and Z4, whereas dCP enhancers contain H3K4me1 and are more enriched for Rad21 and Fs(1)h-L. Additionally, we map the interactions of each enhancer class utilizing a Hi-C dataset with <1 kb resolution. Results suggest that hkCP enhancers are more likely to form multi-TSS interaction networks and be associated with topologically associating domain (TAD) borders, while dCP enhancers are more often bound to one or two TSSs and are enriched at chromatin loop anchors. The data support a model suggesting that the unique architectural protein occupancy within enhancers is one contributor to enhancer-promoter interaction specificity.
authors.affiliation: Department of Biology, Emory University, 1510 Clifton Rd NE, Atlanta, GA 30322, USA.
authors.forename: Caelin
authors.initials: C
authors.lastname: Cubeñas-Potts
authors.affiliation: Department of Biology, Emory University, 1510 Clifton Rd NE, Atlanta, GA 30322, USA.
authors.forename: M Jordan
authors.initials: MJ
authors.lastname: Rowley
authors.affiliation: Department of Biology, Emory University, 1510 Clifton Rd NE, Atlanta, GA 30322, USA.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Lyu
authors.affiliation: Department of Biology, Emory University, 1510 Clifton Rd NE, Atlanta, GA 30322, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Nuclear Organization and Gene Expression Section, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Elissa P
authors.initials: EP
authors.lastname: Lei
authors.affiliation: Department of Biology, Emory University, 1510 Clifton Rd NE, Atlanta, GA 30322, USA.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Corces
mesh_terms: D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding
chemical_list: D015415:Biomarkers; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones