Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.

ABSTRACT: The disruptor of telomeric silencing 1-like (DOT1L) mediates methylation of histone H3 at position lysine 79 (H3K79). Conditional knockout of Dot1l in mouse cerebellar granule cells (Dot1l-cKO^Atoh1) led to a smaller external granular layer with fewer precursors of granule neurons. Dot1l-cKO^Atoh1 mice had impaired proliferation and differentiation of granular progenitors, which resulted in a smaller cerebellum. Mutant mice showed mild ataxia in motor behavior tests. In contrast, Purkinje cell-specific conditional knockout mice showed no obvious phenotype. Genome-wide transcription analysis of Dot1l-cKO^Atoh1 cerebella using microarrays revealed changes in genes that function in cell cycle, cell migration, axon guidance, and metabolism. To identify direct DOT1

SUBMITTER: Bovio PP 

PROVIDER: S-EPMC6505521 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature