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 also found to interact and colocalize with CHD1 in both 
cytoplasmic and nuclear extracts of pancreatic cancer cells. Further, reduced 
level of CHD1 localization in the nucleus in hPaf1/PD2 Knockdown cells could be 
rescued by ectopic expression of hPaf1/PD2. Micrococcal nuclease digestion 
showed an altered chromatin structure in hPaf1/PD2-KD cells. Overall, our 
results suggest that hPaf1/PD2 in association with MLL1 regulates methylation of 
H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin 
remodeling protein CHD1, facilitating its function in pancreatic cancer cells.