PXD030307

PXD030307 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	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:12:42.480.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-11 15:23:18	ID requested
1	2023-10-24 13:46:54	announced
⏵ 2	2023-11-14 09:12:45	announced	2023-11-14: Updated project metadata.

Mehta S, Buyanbat A, Kai Y, Karayel O, Goldman SR, Seruggia D, Zhang K, Fujiwara Y, Donovan KA, Zhu Q, Yang H, Nabet B, Gray NS, Mann M, Fischer ES, Adelman K, Orkin SH, Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells. Cell Chem Biol, 29(8):1273-1287.e8(2022) [pubmed]

submitter keyword: proteomics, data-independent acqusition,PROTAC, mass spectrometry, BCL11A, hemoglobinopathies

Matthias Mann
contact affiliation	Head of the department of Proteomics and Signal Transduction at the MPI of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030307
     1. Label: PRIDE project
     2. Name: Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells