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

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)9783-9798
Number of pages16
JournalNucleic Acids Research
Volume49
Issue number17
Early online date27 Aug 2021
DOIs
Accepted/In press16 Aug 2021
E-pub ahead of print27 Aug 2021
Published27 Sep 2021

Bibliographical note

Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

King's Authors

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.

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