Messenger RNA expression profiling in L3mbtl3 WT versus L3mbtl3 KO/+ mouse cerebella.
The NOTCH/RBPJ pathway governs cell proliferation in many biological contexts, including SHH and Group#3 medulloblastoma (MB) tumorigenesis. Using our proteomic platform, we discovered an interaction between RBPJ, a key co-factor of NOTCH for the modulation of the NOTCH/RBPJ signaling pathway, and L3MBTL3, a methyllysine reader. L3MBTL3 is recruited by RBPJ on chromatin at the enhancers of NOTCH/RBPJ target genes to repress their expression. Deletions of the L3MBTL3 locus are observed in patients with WNT and Group#3 MB and expression of L3MBTL3 in the SHH MB-derived cell DAOY inhibits cell growth, suggesting a putative tumor suppressor role for L3MBTL3 in MB. To further investigate the putative role of L3MBTL3 as a suppressor of MB tumorigenesis, we explored the transcriptome of L3mbtl3 KO mouse cerebella using RNA-seq. Overall design: RNA was obtained from P15 mouse cerebella, three (3) from wild-type and four (4) from 4 L3mbtl3 KO/+ mice.