Selective Activation of CNS and Reference <i>PPARGC1A</i> Promoters Is Associated with Distinct Gene Programs Relevant for Neurodegenerative Diseases.

ABSTRACT: The transcriptional regulator peroxisome proliferator activated receptor gamma coactivator 1A (PGC-1α), encoded by PPARGC1A, has been linked to neurodegenerative diseases. Recently discovered CNS-specific PPARGC1A transcripts are initiated far upstream of the reference promoter, spliced to exon 2 of the reference gene, and are more abundant than reference gene transcripts in post-mortem human brain samples. The proteins translated from the CNS and reference transcripts differ only at their N-terminal regions. To dissect functional differences between CNS-specific isoforms and reference proteins, we used clustered regularly interspaced short palindromic repeats transcriptional activation (CRISPRa) for selective endogenous activation of the CNS or the reference promoters in SH-

SUBMITTER: Kwik M 

PROVIDER: S-EPMC8036390 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature