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BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state.
Xiao, Muran; Kondo, Shinji; Nomura, Masaki; Kato, Shinichiro; Nishimura, Koutarou; Zang, Weijia; Zhang, Yifan; Akashi, Tomohiro; Viny, Aaron; Shigehiro, Tsukasa; Ikawa, Tomokatsu; Yamazaki, Hiromi; Fukumoto, Miki; Tanaka, Atsushi; Hayashi, Yasutaka; Koike, Yui; Aoyama, Yumi; Ito, Hiromi; Nishikawa, Hiroyoshi; Kitamura, Toshio; Kanai, Akinori; Yokoyama, Akihiko; Fujiwara, Tohru; Goyama, Susumu; Noguchi, Hideki; Lee, Stanley C; Toyoda, Atsushi; Hinohara, Kunihiko; Abdel-Wahab, Omar; Inoue, Daichi.
Afiliación
  • Xiao M; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Kondo S; Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Nomura M; Center for Genome Informatics, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, National Institute of Genetics, Mishima, Japan.
  • Kato S; Advanced Genomics Center, National Institute of Genetics, Mishima, Japan.
  • Nishimura K; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Zang W; Facility for iPS Cell Therapy, CiRA Foundation, Kyoto, Japan.
  • Zhang Y; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Akashi T; Institute for Advanced Study, Nagoya University, Nagoya, Japan.
  • Viny A; Center for 5D Cell Dynamics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Shigehiro T; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Ikawa T; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Yamazaki H; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Fukumoto M; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Tanaka A; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Hayashi Y; Center for 5D Cell Dynamics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Koike Y; Division of Systems Biology, Center for Neurological Diseases and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
  • Aoyama Y; Department of Medicine, Division of Hematology and Oncology, and Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
  • Ito H; Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
  • Nishikawa H; Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
  • Kitamura T; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Kanai A; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Yokoyama A; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Fujiwara T; Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • Goyama S; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Noguchi H; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Lee SC; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Toyoda A; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Hinohara K; Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • Abdel-Wahab O; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Inoue D; Institute for Advanced Study, Nagoya University, Nagoya, Japan.
Nat Commun ; 14(1): 8372, 2023 Dec 15.
Article en En | MEDLINE | ID: mdl-38102116
ABSTRACT
ATP-dependent chromatin remodeling SWI/SNF complexes exist in three subcomplexes canonical BAF (cBAF), polybromo BAF (PBAF), and a newly described non-canonical BAF (ncBAF). While cBAF and PBAF regulate fates of multiple cell types, roles for ncBAF in hematopoietic stem cells (HSCs) have not been investigated. Motivated by recent discovery of disrupted expression of BRD9, an essential component of ncBAF, in multiple cancers, including clonal hematopoietic disorders, we evaluate here the role of BRD9 in normal and malignant HSCs. BRD9 loss enhances chromatin accessibility, promoting myeloid lineage skewing while impairing B cell development. BRD9 significantly colocalizes with CTCF, whose chromatin recruitment is augmented by BRD9 loss, leading to altered chromatin state and expression of myeloid-related genes within intact topologically associating domains. These data uncover ncBAF as critical for cell fate specification in HSCs via three-dimensional regulation of gene expression and illuminate roles for ncBAF in normal and malignant hematopoiesis.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromatina Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Factores de Transcripción / Cromatina Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Japón