Requisite Chromatin Remodeling for Myeloid and Erythroid Lineage Differentiation from Erythromyeloid Progenitors
Jun Wu,
Karen Krchma,
Hyung Joo Lee,
Sairam Prabhakar,
Xiaoli Wang,
Haiyong Zhao,
Xiaoyun Xing,
Rho H. Seong,
Daved H. Fremont,
Maxim N. Artyomov,
Ting Wang,
Kyunghee Choi
Affiliations
Jun Wu
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Karen Krchma
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Hyung Joo Lee
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
Sairam Prabhakar
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Xiaoli Wang
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Haiyong Zhao
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Xiaoyun Xing
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
Rho H. Seong
Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea
Daved H. Fremont
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Maxim N. Artyomov
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Ting Wang
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
Kyunghee Choi
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Graduate School of Biotechnology, Kyung Hee University, Yong In, Korea; Corresponding author
Summary: 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.
