HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis

Bowen Yan, Jennifer Yang, Min Young Kim, Huacheng Luo, Nicholas Cesari, Tao Yang, John Strouboulis, Jiwang Zhang, Ross Hardison, Suming Huang, Yi Qiu

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The activity of hematopoietic factor GATA-1 is modulated through p300/CBP-mediated acetylation and FOG-1 mediated indirect interaction with HDAC1/2 containing NuRD complex. Although GATA-1 acetylation is implicated in GATA-1 activation, the role of deacetylation is not studied. Here, we found that the FOG-1/NuRD does not deacetylate GATA-1. However, HDAC1/2 can directly bind and deacetylate GATA-1. Two arginine residues within the GATA-1 linker region mediates direct interaction with HDAC1. The arginine to alanine mutation (2RA) blocks GATA-1 deacetylation and fails to induce erythroid differentiation. Gene expression profiling and ChIP-seq analysis further demonstrate the importance of GATA-1 deacetylation for gene activation and chromatin recruitment. GATA-12RA knock-in (KI) mice suffer mild anemia and thrombocytopenia with accumulation of immature erythrocytes and megakaryocytes in bone marrow and spleen. Single cell RNA-seq analysis of Lin- cKit+ (LK) cells further reveal a profound change in cell subpopulations and signature gene expression patterns in HSC, myeloid progenitors, and erythroid/megakaryocyte clusters in KI mice. Thus, GATA-1 deacetylation and its interaction with HDAC1 modulates GATA-1 chromatin binding and transcriptional activity that control erythroid/megakaryocyte commitment and differentiation.

Original languageEnglish (US)
Pages (from-to)9783-9798
Number of pages16
JournalNucleic acids research
Volume49
Issue number17
DOIs
StatePublished - Sep 27 2021

All Science Journal Classification (ASJC) codes

  • Genetics

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