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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011293-01
Application #
8175355
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2010
Total Cost
$375,458
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Sinclair, Wilson R; Arango, Daniel; Shrimp, Jonathan H et al. (2017) Profiling Cytidine Acetylation with Specific Affinity and Reactivity. ACS Chem Biol 12:2922-2926
Nanan, Kyster K; Ocheltree, Cody; Sturgill, David et al. (2017) Independence between pre-mRNA splicing and DNA methylation in an isogenic minigene resource. Nucleic Acids Res 45:12780-12797
Marina, Ryan J; Oberdoerffer, Shalini (2016) Epigenomics meets splicing through the TETs and CTCF. Cell Cycle 15:1397-9
Marina, Ryan J; Sturgill, David; Bailly, Marc A et al. (2016) TET-catalyzed oxidation of intragenic 5-methylcytosine regulates CTCF-dependent alternative splicing. EMBO J 35:335-55
Oberdoerffer, Shalini (2012) A conserved role for intragenic DNA methylation in alternative pre-mRNA splicing. Transcription 3:106-9
Shukla, Sanjeev; Oberdoerffer, Shalini (2012) Co-transcriptional regulation of alternative pre-mRNA splicing. Biochim Biophys Acta 1819:673-83