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