PXD068470-1

PXD068470 is an original dataset announced via ProteomeXchange.

Title	GABPA recruits the Integrator endonuclease complex to promote transcription elongation
Description	Transcription factors (TFs) coordinate gene regulatory programs essential for cell identity, yet how individual TFs modulate distinct steps of transcription cycle remains incompletely understood. GA-binding protein alpha (GABPA), an erythroblast transformation specific (ETS)-family TF, is crucial for naïve pluripotency during mouse preimplantation development, but its molecular functions remain elusive. Using an acute protein degradation system, we dissected GABPA activity with high temporal resolution, thereby identifying its primary transcriptional targets and underlying mechanisms while minimizing the secondary effects associated with conventional gene knockout approaches. We found that GABPA is essential for mouse embryonic stem cell (mESC) viability through a previously unrecognized mechanism independent of its canonical heterotetrameric partner, GABPB. Mechanistically, GABPA physically interacts with the INTS4/9/11 endonuclease module of the Integrator complex to promote the productive elongation of RNA polymerase II (Pol II) at genes involved in ribonucleoprotein complex biogenesis. Acute loss of GABPA leads to the accumulation of promoter-proximal Pol II and a reduction in Ser2-phosphorylated Pol II across gene bodies, indicating defective transcriptional elongation, whereas prolonged depletion leads to a broader collapse of transcription-associated chromatin features and the general transcription machinery. Together, our study redefines GABPA as a multifaceted transcriptional regulator that acts independently of GABPB and provides a framework for the temporally resolved analysis of TF function in stem cell biology.
HostingRepository	PRIDE
AnnounceDate	2026-08-04
AnnouncementXML	Submission_2026-08-03_20:18:44.341.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hang Yang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-17 22:03:54	ID requested
⏵ 1	2026-08-03 20:18:45	announced

10.1016/j.scib.2026.07.060;

Yang H, Geng J, Yu H, Lu D, Zhao H, Baqie W, Chen Y, Chen FX, Zhang C, GABPA recruits the Integrator endonuclease complex to promote transcription elongation. Sci Bull (Beijing), ():(2026) [pubmed]

submitter keyword: INTAC,GABPA, transcription elongation

Chunxia Zhang
contact affiliation	Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
contact email	cxzhang@genetics.ac.cn
lab head
Hang Yang
contact affiliation	CAS
contact email	hangyang@genetics.ac.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068470
     1. Label: PRIDE project
     2. Name: GABPA recruits the Integrator endonuclease complex to promote transcription elongation