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- W2024520070 abstract "Interplay among GATA transcription factors is an important determinant of cell fate during hematopoiesis. Although GATA-2 regulates hematopoietic stem cell function, mechanisms controlling GATA-2 expression are undefined. Of particular interest is the repression of GATA-2, because sustained GATA-2 expression in hematopoietic stem and progenitor cells alters hematopoiesis. GATA-2 transcription is derepressed in erythroid precursors lacking GATA-1, but the underlying mechanisms are unknown. Using chromatin immunoprecipitation analysis, we show that GATA-1 binds a highly restricted upstream region of the approximately 70-kb GATA-2 domain, despite >80 GATA sites throughout the domain. GATA-2 also binds this region in the absence of GATA-1. Genetic complementation studies in GATA-1-null cells showed that GATA-1 rapidly displaces GATA-2, which is coupled to transcriptional repression. GATA-1 also displaces CREB-binding protein (CBP), despite the fact that GATA-1 binds CBP in other contexts. Repression correlates with reduced histone acetylation domain-wide, but not altered methylation of histone H3 at lysine 4. The GATA factor-binding region exhibited cell-type-specific enhancer activity in transient transfection assays. We propose that GATA-1 instigates GATA-2 repression by means of disruption of positive autoregulation, followed by establishment of a domain-wide repressive chromatin structure. Such a mechanism is predicted to be critical for the control of hematopoiesis." @default.
- W2024520070 created "2016-06-24" @default.
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- W2024520070 creator A5043613674 @default.
- W2024520070 creator A5063330165 @default.
- W2024520070 date "2003-07-11" @default.
- W2024520070 modified "2023-10-11" @default.
- W2024520070 title "GATA-1-dependent transcriptional repression of <i>GATA-2</i> via disruption of positive autoregulation and domain-wide chromatin remodeling" @default.
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- W2024520070 doi "https://doi.org/10.1073/pnas.1432147100" @default.
- W2024520070 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/166395" @default.
- W2024520070 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12857954" @default.
- W2024520070 hasPublicationYear "2003" @default.
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