@article{464e4bd514634c3cbcd96933fedff0d9,
title = "Requisite Chromatin Remodeling for Myeloid and Erythroid Lineage Differentiation from Erythromyeloid Progenitors",
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. The mammalian chromatin-remodeling BAF (BRG1/BRM-associated factor) complex has an essential role in developmental and pathological processes. Wu et al. show that BAF-mediated chromatin remodeling and activation of the myeloid and definitive erythroid transcriptional program at the EMP stage is critical for myeloid and definitive erythroid lineage development.",
keywords = "Baf155, Brg1, Erythromyeloid progenitor, Kdm6a/6b, PU.1, Yolk sac, definitive erythroid, myeloid, p300",
author = "Jun Wu and Karen Krchma and Lee, {Hyung Joo} and Sairam Prabhakar and Xiaoli Wang and Haiyong Zhao and Xiaoyun Xing and Seong, {Rho H.} and Fremont, {Daved H.} and Artyomov, {Maxim N.} and Ting Wang and Kyunghee Choi",
note = "Funding Information: We thank the Choi lab members for constructive criticism and support. We also thank the Washington University Pathology FACS core. This work was supported by NIH grants R01HL55337 and R01HL149954 (to K.C) and the Edward Mallinckrodt Foundation (to K.C. and D.H.F.). Funding Information: We thank the Choi lab members for constructive criticism and support. We also thank the Washington University Pathology FACS core. This work was supported by NIH grants R01HL55337 and R01HL149954 (to K.C) and the Edward Mallinckrodt Foundation (to K.C. and D.H.F.). J.W. K.K. and K.C. conceived and designed experiments and wrote the paper. J.W. and K.K. performed the experiments and analyzed the data. H.J.L. and X.X. performed and analyzed the ATAC-seq data. H.Z. S.P. and M.N.A. performed and analyzed the scRNA-seq data. R.H.S. provided the Baf155f/f mice. X.W. and D.H.F. performed BAF155 and PU.1 immunoprecipitation and western blot analyses. S.P. H.J.L. M.N.A. and T.W. helped write the manuscript. K.C. provided overall supervision and coordinated all experimental activities. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = nov,
day = "17",
doi = "10.1016/j.celrep.2020.108395",
language = "English",
volume = "33",
journal = "Cell Reports",
issn = "2211-1247",
number = "7",
}