PXD026484-1

PXD026484 is an original dataset announced via ProteomeXchange.

Title	Acute depletion of CTCF rewires genome-wide chromatin accessibility
Description	The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studies. However, acute depletion of CTCF globally reduces chromatin interactions but does not significantly alter transcription. Here we systematically integrated multi-omics data including ATAC-seq, RNA-seq, WGBS, Hi-C, Cut&Run, CRISPR-Cas9 survival dropout screening, time-solved deep proteomic and phosphoproteomic analyses in cells carrying auxin-induced degron at endogenous CTCF locus. Acute CTCF protein degradation markedly rewired genome-wide chromatin accessibility. Increased accessible chromatin regions were largely located adjacent to CTCF-binding sites at promoter regions and insulator sites and were associated with enhanced transcription of nearby genes. In addition, we used CTCF-associated multi-omics data to establish a combinatorial data analysis pipeline to discover CTCF co-regulatory partners in regulating downstream gene expression. We successfully identified 40 candidates, including multiple established partners (i.e., MYC) supported by all layers of evidence. Interestingly, many CTCF co-regulators (e.g., YY1, ZBTB7A) that have evident alterations of respective downstream gene expression do not show changes at their expression levels across the multi-omics measurements upon acute CTCF loss, highlighting the strength of our system to discover hidden co-regulatory partners associated with CTCF-mediated transcription. This study highlights CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role in transcriptional regulation
HostingRepository	PRIDE
AnnounceDate	2021-07-04
AnnouncementXML	Submission_2021-07-03_18:14:37.936.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hong Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-04 02:52:40	ID requested
⏵ 1	2021-07-03 18:14:38	announced

Dataset with its publication pending

submitter keyword: CTCF, multiomics, proteome, phosphoproteome,

Hong Wang
contact affiliation	St Jude Children's Research Hospital
contact email	hong.wang@stjude.org
lab head
Hong Wang
contact affiliation	St.Jude children's Research hospi
contact email	hong.wang@stjude.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026484
     1. Label: PRIDE project
     2. Name: Acute depletion of CTCF rewires genome-wide chromatin accessibility