INTS11 regulates hematopoiesis by promoting PRC2 function

Peng Zhang, Pinpin Sui, Shi Chen, Ying Guo, Ying Li, Guo Ge, Ganqian Zhu, Hui Yang, Cody M. Rogers, Patrick Sung, Stephen D. Nimer, Mingjiang Xu, Feng Chun Yang

Research output: Contribution to journalArticlepeer-review

Abstract

INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-specific genetic deletion of Ints11 leads to cell cycle arrest and impairment of fetal and adult HSPCs. We identified a novel INTS11-interacting protein complex, Polycomb repressive complex 2 (PRC2), that maintains HSPC functions. Loss of INTS11 destabilizes the PRC2 complex, decreases the level of histone H3 lysine 27 trimethylation (H3K27me3), and derepresses PRC2 target genes. Reexpression of INTS11 or PRC2 proteins in Ints11-deficient HSPCs restores the levels of PRC2 and H3K27me3 as well as HSPC functions. Collectively, our data demonstrate that INTS11 is an essential regulator of HSPC homeostasis through the INTS11-PRC2 axis.

Original languageEnglish (US)
Article numberabh1684
JournalScience Advances
Volume7
Issue number36
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'INTS11 regulates hematopoiesis by promoting PRC2 function'. Together they form a unique fingerprint.

Cite this