Unknown,Transcriptomics,Genomics,Proteomics

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FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function


ABSTRACT: FOXA1 is a FKHD family protein that translates epigenetic signatures at target enhancers to lineage-specific transcription and differentiation. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of this epigenetic signature, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically, this involves TET1, a 5-methylcytosine dioxygenase. We found that FOXA1 induces TET1 expression via direct binding at its cis-regulatory elements. Further, FOXA1 physically interacts with the TET1 protein through its CXXC domain. TET1 thus co-occupies FOXA1-dependent enhancers and mediates local DNA demethylation and concomitant histone 3 lysine 4 methylation, further potentiating FOXA1 recruitment. FOXA1 binding events were markedly reduced following TET1 depletion. Together, our results support that FOXA1 is not only a reader, but also a writer, of the epigenetic signatures at lineage-specific enhancers and that TET1 and FOXA1 form a feed-forward regulatory loop for enhancer activation. ChIP-Seq examination of FOXA1 binding sites in LNCaP cell, and epigenetic markers (5mC, 5hmC, H3K4me2) profiling upon TET1 depletion

ORGANISM(S): Homo sapiens

SUBMITTER: Jindan Yu 

PROVIDER: E-GEOD-73363 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function.

Yang Yeqing A YA   Zhao Jonathan C JC   Fong Ka-Wing KW   Kim Jung J   Li Shangze S   Song Chunxiao C   Song Bing B   Zheng Bin B   He Chuan C   Yu Jindan J  

Nucleic acids research 20160601 17


Forkhead box A1 (FOXA1) is an FKHD family protein that plays pioneering roles in lineage-specific enhancer activation and gene transcription. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of these epigenetic signatures, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically, this involves TET1, a 5-methylcytosine dioxygenase. We found that FOXA1 induces TET1 expression via direct binding  ...[more]

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