title: SMARCAL1 Negatively Regulates C-Myc Transcription By Altering The Conformation Of The Promoter Region.
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.
authors.affiliation: School of Life Sciences, JNU, New Delhi 110067.
authors.forename: Tapan
authors.initials: T
authors.lastname: Sharma
authors.affiliation: School of Life Sciences, JNU, New Delhi 110067.
authors.forename: Ritu
authors.initials: R
authors.lastname: Bansal
authors.affiliation: School of Life Sciences, JNU, New Delhi 110067.
authors.forename: Dominic Thangminlen
authors.initials: DT
authors.lastname: Haokip
authors.affiliation: School of Life Sciences, JNU, New Delhi 110067.
authors.forename: Isha
authors.initials: I
authors.lastname: Goel
authors.affiliation: School of Life Sciences, JNU, New Delhi 110067.
authors.forename: Rohini
authors.initials: R
authors.lastname: Muthuswami
mesh_terms: D000818:Animals; D002417:Cattle; D004265:DNA Helicases / Q000378:metabolism*; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D023061:Gene Order; D016259:Genes, myc; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; D012319:RNA Polymerase II; C412482:SMARCAL1 protein, human; C084108:SMARCA4 protein, human; D004265:DNA Helicases