Epigenetic regulation of presenilin 1 and 2 in the cerebral cortex of mice during development.

Previously, we reported differential expression profile of Presenilin (PS)1 and 2 and their interacting partners in mouse cerebral cortex during development. Our findings indicated crucial involvement of these proteases in prenatal and postnatal development of mouse cerebral cortex. However, the mechanisms that precisely control their expression in stage-specific manner during brain development are still elusive. In this regard, epigenetic modifications by DNA methylation and histone acetylation during brain development deserve major attention. Therefore, we have analyzed the epigenetic regulation of PS1 and PS2 in mouse cerebral cortex during development. The data demonstrated a good correspondence of H3K9/14 Ac level in PS1 and PS2 promoter with their expression profile during cerebral cortical development. H3K9/14 Ac level was high at embryonic day (E)12.5, declined at E18.5, increased from postnatal day (P)0 to P45 and decreased again at 20 weeks (w) in PS1 promoter. For PS2, H3K9/14 Ac level was high at E12.5, thereafter, reduced upto P20 and increased at P45 and 20 weeks. DNA methylation sites also varied in number and position at different developmental stages, and some of them are putative sites for binding of transcription factors like HSF-1, Ets-1, and Sp1 that are crucial for brain developmental processes, as revealed by in silico analysis. Though MeCP2 level also altered during development, they did not correlate with PS1 and PS2 expression profile. Taken together, our findings provide the first evidence of epigenetic regulation of PS1 and PS2 by H3K9/14 histone acetylation and DNA methylation in mouse cerebral cortex during development.