Mammalian chromatin remodeling complex SWI/SNF is essential for enhanced expression of the albumin gene during liver development

Yujin Inayoshi, Katsuhide Miyake, Yuichi Machida, Hidenori Kaneoka, Masaomi Terajima, Takeaki Dohda, Mikio Takahashi, Shinji Iijima

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The chromatin remodeling complex SWI/SNF is known to regulate the transcription of several genes by controlling chromatin structure in an ATP-dependent manner. SWI/SNF contains the Swi2p/Snf2p like ATPases BRG1 or BRM exclusively. We found that the expression of BRM gradually increases and that of BRG1 decreases as liver cells differentiate. Chromatin immunoprecipitation assays revealed that the ATPase subunits of SWI/SNF and tumor suppressor retinoblastoma (RB) family proteins bind to the promoter region of the albumin gene in hepatocytes, and that the replacement of BRG1 with BRM and pRB with p130 at this site occurs over the course of differentiation. Small interfering RNA experiments showed that blocking the expression of BRG1 and BRM in fetal and adult hepatocytes, respectively, causes a reduction in albumin expression. In luciferase reporter assays with a pREP4-based reporter plasmid that forms a chromatin structure, BRG1 showed activity stimulating the expression of the albumin promoter mediated by CCAAT/enhancer-binding protein α (C/EBPα). This enhancement was facilitated by the RB family members pRB and p130. ATPase assays showed that both pRB and C/EBPα proteins directly stimulate the ATPase activity of BRG1. Our findings suggest that the mechanism by which the activity of transcription factors is enhanced by RB family members and SWI/SNF includes an increase in the ATPase activity of the chromatin remodeling complex.

Original languageEnglish (US)
Pages (from-to)177-188
Number of pages12
JournalJournal of Biochemistry
Volume139
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • Albumin
  • CCAAT/enhancer-binding protein α
  • Primary hepatocytes
  • Retinoblastoma protein
  • SWI/SNF

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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