Long-term memory consolidation is a tightly regulated process that requires de novo gene expression and protein synthesis. The transcriptional co-repressor Sin3A functions as a scaffold to mediate association of chromatin remodeling proteins including histone deacetylase (HDAC) with transcription factors and regulatory complexes. Mammalian Sin3A proteins, mSin3A, act as adapter molecules which bind both to repressive transcription factors and to the methyl-CpG-binding proteins (MeCP2) and recruit HDAC to assemble a multiprotein repressor complex. Similar to a genetic or pharmacological inhibition of HDAC, mSin3A mutation produces robust long-term memory enhancements in multiple rodent learning paradigms.
Our ongoing projects focus more specifically on:
-The genes which are regulated by mSin3A co-repressor during memory consolidation
-The dynamics of proteins recruitment orchestrated by mSin3A
-The epigenetic marks which are targeted by mSin3A
-The role of mSin3A co-repressor in age-related cognitive decline (collaboration CPTP: Cécile Malnou)