Nzf2 promotes oligodendrocyte differentiation and regeneration via repressing HDAC1-mediated histone deacetylation.

ABSTRACT: Proper axonal myelination and function of the vertebrate central nervous system rely largely on the timely differentiation of oligodendrocytes (OLs), yet key regulatory factors remain enigmatic. Our study reveals neural zinc finger (Nzf2) as a crucial orchestrator that controls the timing of OL differentiation both during development and myelin repair, contrasting with its previously suggested role in direct myelin gene regulation. Nzf2 ablation delays the onset of OL differentiation, while hyperactivation stimulates OL differentiation both during development and remyelination. Using RNA-seq and ChIP-seq, we pinpoint Nkx2.2 as a critical downstream target of Nzf2. Specific binding of Nzf2 in the Nkx2.2 gene locus inhibits histone deacetylation by disrupting the HDAC1 represso

SUBMITTER: Xu X 

PROVIDER: S-EPMC11641009 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature