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Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells [PRO-seq washout]

ABSTRACT: Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells [PRO-seq washout]

PROVIDER: PRJNA800361 | ENA |

REPOSITORIES: ENA

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Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells [PRO-seq washout]

Project description:We acutely depleted the BCL11A protein by using the dTAG PROTAC technology, then performed a drug washout and and assessed its immediate consequences nascent transcription.

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Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells

Project description:Reactivation of fetal hemoglobin expression by down-regulation of BCL11A is a promising treatment of -hemoglobinopathies. A detailed understanding of BCL11A-mediated repression of -globin gene (HBG1/2) transcription is lacking, as studies to date used perturbations by shRNA or CRISPR/Cas9 gene editing. We leveraged the dTAG PROTAC platform to acutely deplete BCL11A protein in erythroid cells and examined consequences by PRO-seq, proteomics, chromatin accessibility, and histone profiling. Among ≤ 31 genes repressed by BCL11A, HBG1/2 and HBZ show the most abundant and progressive changes in transcription and chromatin accessibility upon BCL11A loss. Transcriptional changes at HBG1/2 were detected in < 2h. Robust HBG1/2 reactivation upon acute BCL11A-depletion occurred without loss of promoter 5methylcytosine (5mC). Using targeted protein degradation, we establish a hierarchy of gene reactivation at BCL11A targets, in which nascent transcription is followed by increased chromatin accessibility, and both are uncoupled from promoter DNA methylation at the HBG1/2 loci.

2023-10-24 | PXD030307 | Pride

Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells

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Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells [ChIP-seq]

Project description:We acutely depleted the BCL11A protein by using the dTAG PROTAC technology, and assessed its consequences on histone modification by ChIP-seq,and compared this to changes in nascent transcription, DNA methylation, Protein expression and chromatin accessibility.

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Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells

Project description:Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells

| PRJNA800348 | ENA

Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells [ATAC-seq]

Project description:Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells [ATAC-seq]

| PRJNA800359 | ENA

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