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HRI activates ATF4 to promote BCL11A transcription and fetal hemoglobin silencing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE143963 | GEO | 2020/04/17

REPOSITORIES: GEO

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The HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression.

Project description: Not available

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HRI activates ATF4 to promote BCL11A transcription and fetal hemoglobin silencing [Capture-C]

Project description:Through a CRISPR-Cas9 guided loss-of-function screen in human erythroid cells we identified transcription factor ATF4, a known HRI-regulated protein, as a novel γ-globin repressor. ATF4 binds to a BCL11A enhancer to augment promoter contacts, stimulates BCL11A transcription to repress γ-globin expression. Notably, mice deficient for HRI displayed normal Bcl11a levels, suggesting species selective regulation that we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable. This illustrates potential limits of commonly used murine models of globin gene regulation.

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HRI activates ATF4 to promote BCL11A transcription and fetal hemoglobin silencing [ChIP-seq]

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