2. Academic Validation
  3. Requisite Chromatin Remodeling for Myeloid and Erythroid Lineage Differentiation from Erythromyeloid Progenitors

Requisite Chromatin Remodeling for Myeloid and Erythroid Lineage Differentiation from Erythromyeloid Progenitors

  • Cell Rep. 2020 Nov 17;33(7):108395. doi: 10.1016/j.celrep.2020.108395.
Jun Wu 1,  Karen Krchma 1,  Hyung Joo Lee 2,  Sairam Prabhakar 1,  Xiaoli Wang 1,  Haiyong Zhao 1,  Xiaoyun Xing 2,  Rho H Seong 3,  Daved H Fremont 1,  Maxim N Artyomov 1,  Ting Wang 4,  Kyunghee Choi 5
Affiliations

Affiliations

  • 1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • 2 Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
  • 3 Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
  • 4 Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA.
  • 5 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Graduate School of Biotechnology, Kyung Hee University, Yong In, Korea. Electronic address: kchoi@wustl.edu.
PMID: 33207205 DOI: 10.1016/j.celrep.2020.108395
Abstract

The mammalian SWitch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling BAF (BRG1/BRM-associated factor) complex plays an essential role in developmental and pathological processes. We show that the deletion of Baf155, which encodes a subunit of the BAF complex, in the Tie2(+) lineage (Baf155 (CKO) leads to defects in yolk sac myeloid and definitive erythroid (EryD) lineage differentiation from erythromyeloid progenitors (EMPs). The chromatin of myeloid gene loci in Baf155 CKO EMPs is mostly inaccessible and enriched mainly by the ETS binding motif. BAF155 interacts with PU.1 and is recruited to PU.1 target gene loci together with p300 and KDM6a. Treatment of Baf155 CKO embryos with GSK126, an H3K27me2/3 methyltransferase EZH2 Inhibitor, rescues myeloid lineage gene expression. This study uncovers indispensable BAF-mediated chromatin remodeling of myeloid gene loci at the EMP stage. Future studies exploiting Epigenetics in the generation and application of EMP derivatives for tissue repair, regeneration, and disease are warranted.

Keywords

Baf155; Brg1; Erythromyeloid progenitor; Kdm6a/6b; PU.1; Yolk sac; definitive erythroid; myeloid; p300.

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