Unknown,Transcriptomics,Genomics,Proteomics

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Enhancer-bound LDB1 Regulates a Corticotrope Promoter Pausing Repression Program [ChIP-seq]


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 the LIM domain binding protein, LDB1/CLIM2/NLI, interacting with the enhancer binding protein, ASCL1, 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 target gene promoter genes. While LDB1-dependend 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 MTA2, a component of the NuRD 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. ChIP assay followed by high throughput sequencing (ChIP-seq)

ORGANISM(S): Mus musculus

SUBMITTER: MICHAEL ROSENFELD 

PROVIDER: E-GEOD-64483 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Zhang Feng F   Tanasa Bogdan B   Merkurjev Daria D   Lin Chijen C   Song Xiaoyuan X   Li Wenbo W   Tan Yuliang Y   Liu Zhijie Z   Zhang Jie J   Ohgi Kenneth A KA   Krones Anna A   Skowronska-Krawczyk Dorota D   Rosenfeld Michael G MG  

Proceedings of the National Academy of Sciences of the United States of America 20150120 5


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 wit  ...[more]

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