Genomewide approaches for BACH1 target genes in mouse embryonic fibroblasts showed BACH1-Pparg pathway in adipogenesis

Mitsuyo Matsumoto, Keiichi Kondo, Takuma Shiraki, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Nobuo Yaegashi, Hideki Katagiri, Kazuhiko Igarashi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)553-567
Number of pages15
JournalGenes to Cells
Volume21
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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