PXD042681

PXD042681 is an original dataset announced via ProteomeXchange.

Title	The PURB-HOTAIR complex regulates p53-dependent promoter-specific transcriptional activation
Description	p53 executes its diverse functions via different transcriptional targets, but the precise mechanism of promoter-specific regulation by p53 remains largely unknown. Through biochemical purification, we identify PURB, a dual DNA/RNA-binding protein, which acts as a transcriptional co-repressor for p53 in a manner dependent on p53 acetylation status. PURB is overexpressed in human cancers while its knockdown induces p53-dependent activation of p21 but has no effect on other major promoters such as PUMA and Mdm2. In contrast to other p53 corepressors, PURB can recognize a unique DNA element at the p21 promoter, with the loss of this element not affecting p53-mediated transactivation but abrogating the ability of p53 to recruit PURB to the p21 promoter for repression. Mechanistically, PURB requires its sequence-specific binding with lncRNA HOTAIR to exert its repressive role. In turn, HOTAIR interacts directly with EZH2 and, bridged by the PURB/HOTAIR complex, p53 can recruit the EZH2 histone methyltransferase to target promoters for transcriptional repression. Further analysis of p53 targets indicates a number of promoters that may serve as a target for PURB-binding, suggesting that this mechanism of PURB-dependent promoter-specific regulation may not be limited to p21. These data establish a mode of LncRNA-mediated regulation of p53 transcription in a sequence-specific manner and reveal a previously unanticipated mechanism for acetylation-mediated promoter-specific regulation through a cis-regulatory element recognized by the PURB-HOTAIR complex.
HostingRepository	PRIDE
AnnounceDate	2025-06-16
AnnouncementXML	Submission_2025-06-16_06:59:42.395.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042681
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Zhangchuan Xia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-02 09:05:31	ID requested
1	2025-04-23 18:30:41	announced
⏵ 2	2025-06-16 06:59:42	announced	2025-06-16: Updated project metadata.

10.6019/PXD042681;

submitter keyword: long non-coding RNA, cis-regulatory element, epigenetics, promoter-specific regulation, HOTAIR, SUV39H1, tumor suppression, PURB,p53

Dr. Wei Gu
contact affiliation	Department of Pathology and Cell Biology and Institute for Cancer Genetics Herbert Irving Comprehensive Cancer Vagelos College of Physicians & Surgeons Columbia University (lab head)
contact email	wg8@cumc.columbia.edu
lab head
Zhangchuan Xia
contact affiliation	Institute for Cancer Genetics Herbert Irving Comprehensive Cancer Center Vagelos College of Physicians & Surgeons Columbia University
contact email	zx2264@cumc.columbia.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042681
     1. Label: PRIDE project
     2. Name: The PURB-HOTAIR complex regulates p53-dependent promoter-specific transcriptional activation