title: A Bach2-Cebp Gene Regulatory Network for the Commitment of Multipotent Hematopoietic Progenitors.
abstract: Hematopoietic stem cell and multipotent progenitor (MPP) commitment can be tuned in response to an infection so that their differentiation is biased toward myeloid cells. Here, we find that Bach2, which inhibits myeloid differentiation in common lymphoid progenitors, represses a cohort of myeloid genes and activates those linked to lymphoid function. Bach2 repressed both Cebpb and its target Csf1r, encoding C/EBPβ and macrophage colony-stimulating factor receptor (M-CSFr), respectively, whereas C/EBPβ repressed Bach2 and activated Csf1r. Bach2 and C/EBPβ further bound to overlapping regulatory regions at their myeloid target genes, suggesting the presence of a gene regulatory network (GRN) with mutual repression between these factors and a feedforward loop leading to myeloid gene regulation. Lipopolysaccharide reduced the expression of Bach2, resulting in enhanced myeloid differentiation. The Bach2-C/EBPβ GRN pathway thus tunes MPP commitment to myeloid and lymphoid lineages both under normal conditions and after infection.
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan; Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Ari
authors.initials: A
authors.lastname: Itoh-Nakadai
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sasaki
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Uehara
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Ebina-Shibuya
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Morooka
authors.affiliation: Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Cell Proliferation, United Center for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.affiliation: Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Cell Proliferation, United Center for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan; Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan; Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: igarashi@med.tohoku.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D053263:Gene Regulatory Networks; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding
chemical_list: C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D022762:CCAAT-Enhancer-Binding Proteins
keywords: B cells; gene regulatory network; infection; inner myeloid; lineage commitment; multipotent progenitors; stem cells; super enhancers; transcription factors