SMARCAL1 Negatively Regulates C-Myc Transcription By Altering The Conformation Of The Promoter Region

Sci Rep. 2015 Dec 9:5:17910. doi: 10.1038/srep17910.

Abstract

SMARCAL1, a member of the SWI2/SNF2 protein family, stabilizes replication forks during DNA damage. In this manuscript, we provide the first evidence that SMARCAL1 is also a transcriptional co-regulator modulating the expression of c-Myc, a transcription factor that regulates 10-15% genes in the human genome. BRG1, SMARCAL1 and RNAPII were found localized onto the c-myc promoter. When HeLa cells were serum starved, the occupancy of SMARCAL1 on the c-myc promoter increased while that of BRG1 and RNAPII decreased correlating with repression of c-myc transcription. Using Active DNA-dependent ATPase A Domain (ADAAD), the bovine homolog of SMARCAL1, we show that the protein can hydrolyze ATP using a specific region upstream of the CT element of the c-myc promoter as a DNA effector. The energy, thereby, released is harnessed to alter the conformation of the promoter DNA. We propose that SMARCAL1 negatively regulates c-myc transcription by altering the conformation of its promoter region during differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • DNA Helicases / metabolism*
  • G-Quadruplexes
  • Gene Expression Regulation*
  • Gene Order
  • Genes, myc*
  • Humans
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation
  • Promoter Regions, Genetic*
  • Protein Binding
  • RNA Polymerase II / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • Nuclear Proteins
  • Transcription Factors
  • RNA Polymerase II
  • SMARCAL1 protein, human
  • SMARCA4 protein, human
  • DNA Helicases