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Publication : Epigenome profiling and editing of neocortical progenitor cells during development.

First Author  Albert M Year  2017
Journal  EMBO J Volume  36
Issue  17 Pages  2642-2658
PubMed ID  28765163 Mgi Jnum  J:252135
Mgi Id  MGI:6094590 Doi  10.15252/embj.201796764
Citation  Albert M, et al. (2017) Epigenome profiling and editing of neocortical progenitor cells during development. EMBO J 36(17):2642-2658
abstractText  The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator Eomes We use catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the Eomes locus in vivo, which results in reduced Tbr2 expression and lower basal progenitor abundance, underscoring the relevance of dynamic H3K27me3 changes during neocortex development. Taken together, we provide a rich resource of neocortical histone methylation data and outline an approach to investigate its contribution to the regulation of selected genes during neocortical development.
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