The protein Vezf1 plays multiple roles important for embryonic development. In 
Vezf1(-/-) mouse embryonic stem (mES) cells, our earlier data showed widespread 
changes in gene-expression profiles, including decreased expression of the 
full-length active isoform of Dnmt3b methyltransferase and concomitant 
genome-wide reduction in DNA methylation. Here we show that in HeLaS3 cells 
there is a strong genome-wide correlation between Vezf1 binding and peaks of 
elongating Ser2-P RNA polymerase (Pol) ll, reflecting Vezf1-dependent slowing of 
elongation. In WT mES cells, the elongating form of RNA pol II accumulates near 
Vezf1 binding sites within the dnmt3b gene and at several other Vezf1 sites, and 
this accumulation is significantly reduced at these sites in Vezf1(-/-) mES 
cells. Depending upon genomic location, Vezf1-mediated Pol II pausing can have 
different regulatory roles in transcription and splicing. We find examples of 
genes in which Vezf1 binding sites are located near cassette exons, and in which 
loss of Vezf1 leads to a change in the relative abundance of alternatively 
spliced messages. We further show that Vezf1 interacts with Mrg15/Mrgbp, a 
protein that recognizes H3K36 trimethylation, consistent with the role of 
histone modifications at alternatively spliced sites.