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Assesment of DOT1L direct targets via ChIP of H3K79me2 at E12.5 of mouse cortex

ABSTRACT: Cortical development is under control of transcriptional programs that are orchestrated by activation of key determinants such as transcription factors. But stable inheritance of temporo-spatial activity of factors influencing cell fate and regionalization in different layers is only partly understood. We report that chromatin methylation at H3K79 transmits cell fate and layering information from early to late progenitors. Activity of DOT1L, mediating H3K79 methylation, prevents premature cell cycle exit by increasing expression of genes regulating asymmetric cell division (Vangl2, Cenpj). Transcriptional programs characteristic for upper layer neurons are less active in Dot1l-deficient mice already at developmental stages that precede upper layer neuron generation. DOT1L activates expression of many key determinants such as Cux1, Cux2, Satb2 or Pou3f3. Additionally, DOT1L affects transcription of Sox family members, suggesting an evolutionary conserved mechanism. In part, DOT1L and H3K79me2 replace inactivating H3K9me3 at Sox family promoters and allow for transcriptional activation during neural differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE95831 | GEO | 2017/12/31

SECONDARY ACCESSION(S): PRJNA378540

REPOSITORIES: GEO

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