title: Genomewide approaches for BACH1 target genes in mouse embryonic fibroblasts showed BACH1-Pparg pathway in adipogenesis.
abstract: The transcription repressor BTB and CNC homology 1 (BACH1) represses genes involved in heme metabolism and oxidative stress response. BACH1 also suppresses the p53-dependent cellar senescence in primary mouse embryonic fibroblasts (MEFs). To investigate the role of BACH1 in MEF other than its known functions, we carried out a genomewide mapping of binding site for BACH1 and its heterodimer partner MAFK in immortalized MEFs (iMEFs) using chromatin immunoprecipitation and next-generation sequencing technology (ChIP-sequence). The comparative analysis of the ChIP-sequence data and DNA microarray data from Bach1-deficient and wild-type (WT) iMEF showed 35 novel candidate target genes of BACH1. Among these genes, five genes (Pparg, Nfia, Ptplad2, Adcy1 and Ror1) were related with lipid metabolism. Bach1-deficient iMEFs showed increased expression of mRNA and protein of PPARγ, which is the key factor of adipogenesis. These cells also showed a concomitant increase in ligand-dependent activation of PPARγ target genes compared with wild-type iMEFs. Moreover, Bach1-deficient iMEFs efficiently differentiated to adipocyte compared with wild-type cells in the presence of PPARγ ligands. Our results suggest that BACH1 regulates expression of adipocyte-related genes including Pparg and potentiates adipocyte differentiation capacity.
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.|Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Division of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.|Faculty of Biology-Oriented Science and Technology, Kinki University, Nishimitani, Kinokawashi, Wakayama, 649-6493, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Shiraki
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Andrey
authors.initials: A
authors.lastname: Brydun
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.affiliation: Division of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, 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, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D050985:MafK Transcription Factor / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D015398:Signal Transduction
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D050985:MafK Transcription Factor; C494696:Mafk protein, mouse; D047495:PPAR gamma