INTS11 regulates hematopoiesis by promoting PRC2 function

• DOI: 10.1126/sciadv.abh1684
• Publication Date: 2021-09-03T18:04:35Z
• Authors: 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
• Keywords: PRC2; Polycomb-group proteins

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