title: Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program.
abstract: Substantial evidence supports the hypothesis that enhancers are critical regulators of cell-type determination, orchestrating both positive and negative transcriptional programs; however, the basic mechanisms by which enhancers orchestrate interactions with cognate promoters during activation and repression events remain incompletely understood. Here we report the required actions of LIM domain-binding protein 1 (LDB1)/cofactor of LIM homeodomain protein 2/nuclear LIM interactor, interacting with the enhancer-binding protein achaete-scute complex homolog 1, to mediate looping to target gene promoters and target gene regulation in corticotrope cells. LDB1-mediated enhancer:promoter looping appears to be required for both activation and repression of these target genes. Although LDB1-dependent activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of metastasis-associated 1 family, member 2, a component of the nucleosome remodeling deacetylase complex, on these negative enhancers, required for the repressive enhancer function. These results indicate that LDB1-dependent looping events can deliver repressive cargo to cognate promoters to mediate promoter pausing events in a pituitary cell type.
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine, mrosenfeld@ucsd.edu fzhang@ucsd.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Tanasa
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine, Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093;
authors.forename: Daria
authors.initials: D
authors.lastname: Merkurjev
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Chijen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine, Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Song
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Li
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ohgi
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Anna
authors.initials: A
authors.lastname: Krones
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine.
authors.forename: Dorota
authors.initials: D
authors.lastname: Skowronska-Krawczyk
authors.affiliation: Howard Hughes Medical Institute and Department of Medicine, School of Medicine, mrosenfeld@ucsd.edu fzhang@ucsd.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000818:Animals; D002460:Cell Line; D052680:Corticotrophs / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D060588:LIM Domain Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic
chemical_list: D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse
keywords: ASCL1; LDB1; MTA2; enhancer; looping