Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program

Feng Zhang, Bogdan Tanasa, Daria Merkurjev, Chijen Lin, Xiaoyuan Song Wenbo Li, Yuliang Tan, Zhijie Liu, Jie Zhang, Kenneth A. Ohgi, Anna Krones, Dorota Skowronska-Krawczyk, Michael G. Rosenfeld

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 LIMinteractor, interactingwith 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.

Original languageEnglish (US)
Pages (from-to)1380-1385
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number5
DOIs
StatePublished - Feb 3 2015

Keywords

  • ASCL1
  • Enhancer
  • LDB1
  • Looping
  • MTA2

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program'. Together they form a unique fingerprint.

Cite this