Impact of chromatin structure on alternative splicing of CD45 pre-mRNA

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

As a postdoctoral fellow, I showed that the heterogeneous ribonucleoprotein L-like (hnRNPLL) was a master regulator of the transition from the CD45RA to CD45RO isoform. I further identified hnRNPLL-expressing BJAB B cells to exclusively express the CD45RO isoform, whereas the hnRNPLL-negative BL41 B cell line exclusively expressed the CD45RA isoform at steady state. I am presently using these cellular model systems to identify differences in chromatin structure that correlate with differential CD45 isoform expression. Our preliminary data show that there is very little difference in the composition of the DNA in both cell types. However, we do find areas of relative enrichment of DNA binding factors, suggesting that chromatin acts to poise the DNA in a particular structure that influences pol II-mediated splicing decisions. These studies have utilized technologies such as Chromatin-immunopreciptiation, lentiviral transduction and flow cytometry.