Abstract
Integrated high-risk human papillomavirus (HPV) DNA was frequently detected in the genomes of cervical carcinoma cells. The HPV E6 and E7 oncoproteins disrupt the functions of tumor suppressors p53 and Rb; thus, understanding the mechanism by which HPV E6 and E7 gene expression is regulated in cancer cells is highly relevant to cancer biology. Brg1 is a catalytic subunit of the SWI/SNF chromatin remodeling complexes that function in the transcriptional regulation of certain cellular genes. Here, we show that knockdown of Brg1 in HeLa cells leads to cell cycle arrest, p53 and Rb protein accumulation and, interestingly, downregulated expression of HPV18 E6 and E7 genes. Brg1 binds the HPV18 LCR in a JunB- and p300-dependent manner and is required for efficient recruitment of RNA polymerase II to the HPV18 LCR. The function of Brg1 in HPV18 gene regulation is unique given that its homolog Brm does not play a role in this regulatory pathway, and this may help design target-specific intervention strategies.
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