PXD030301-1

PXD030301 is an original dataset announced via ProteomeXchange.

Title	Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells
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
HostingRepository	PRIDE
AnnounceDate	2022-07-27
AnnouncementXML	Submission_2022-07-27_11:18:41.971.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-11 15:13:32	ID requested
⏵ 1	2022-07-27 11:18:42	announced
2	2023-11-14 08:53:45	announced	2023-11-14: Updated project metadata.

10.1016/J.CHEMBIOL.2022.06.007;

submitter keyword: dTAG, BCL11A, Degradation, PROTAC

Eric Fischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030301
     1. Label: PRIDE project
     2. Name: Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells