human rna polymerase ii-association factor 1 (hpaf1pd2) regulates histone methylation and chromatin remodeling in pancreatic cancer人类rna聚合酶ii-association因子1(hpaf1pd2)在胰腺癌调节组蛋白甲基化和染色质重塑.pdfVIP

Human RNA Polymerase II-Association Factor 1 (hPaf1/ PD2) Regulates Histone Methylation and Chromatin Remodeling in Pancreatic Cancer 1 1 1 1,2 Parama Dey , Moorthy P. Ponnusamy , Shonali Deb , Surinder K. Batra * 1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America, 2 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America Abstract Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri- methylation at histone H3 lysine 4 residues in pancreatic cancer cells. Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues. Also, a reduction in hPaf1 level resulted in reduced MLL1 expression and a corresponding decrease in the level of CHD1 (Chromohelicase DNA-binding protein 1), an ATPase dependent chromatin remodeling enzyme that specifically binds to H3K4 di and trimethyl marks. hPaf1/PD2 was als