title: The transcription repressors Bach2 and Bach1 promote B cell development by repressing the myeloid program.
abstract: Mature lymphoid cells express the transcription repressor Bach2, which imposes regulation on humoral and cellular immunity. Here we found critical roles for Bach2 in the development of cells of the B lineage, commencing from the common lymphoid progenitor (CLP) stage, with Bach1 as an auxiliary. Overexpression of Bach2 in pre-pro-B cells deficient in the transcription factor EBF1 and single-cell analysis of CLPs revealed that Bach2 and Bach1 repressed the expression of genes important for myeloid cells ('myeloid genes'). Bach2 and Bach1 bound to presumptive regulatory regions of the myeloid genes. Bach2(hi) CLPs showed resistance to myeloid differentiation even when cultured under myeloid conditions. Our results suggest that Bach2 functions with Bach1 and EBF1 to promote B cell development by repressing myeloid genes in CLPs.
authors.affiliation: 1] Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. [2] CREST, Japan Science and Technology Agency, Sendai, Japan.
authors.forename: Ari
authors.initials: A
authors.lastname: Itoh-Nakadai
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Hikota
authors.affiliation: 1] Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. [2] CREST, Japan Science and Technology Agency, Sendai, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.affiliation: RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kometani
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe-Matsui
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tashiro
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Jiying
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory for Immune Regeneration RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Ikawa
authors.affiliation: 1] Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. [2] CREST, Japan Science and Technology Agency, Sendai, Japan. [3] Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: 1] RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. [2] WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: 1] Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. [2] CREST, Japan Science and Technology Agency, Sendai, Japan. [3] Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: C486316:Bach1 protein, mouse; C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; C489921:Ebf1 protein, mouse; D015534:Trans-Activators