RT Journal Article
SR Electronic
T1 Differential chromatin accessibility in developing projection neurons is correlated with transcriptional regulation of cell fate
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 645572
DO 10.1101/645572
A1 Whitney E. Heavner
A1 Shaoyi Ji
A1 James H. Notwell
A1 Ethan S. Dyer
A1 Alex M. Tseng
A1 Johannes Birgmeier
A1 Boyoung Yoo
A1 Gill Bejerano
A1 Susan K. McConnell
YR 2019
UL http://biorxiv.org/content/early/2019/05/21/645572.abstract
AB We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than fifty unique types of mature cortical projection neurons defined by their distinct gene expression profiles. Here we compare gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversity neuron cell fate. We find groups of transcription factors whose expression is correlated with chromatin accessibility, transcription factor binding motifs, and lncRNAs that define each subclass and validate the function of a family of novel candidate genes in vitro. Our multidimensional approach reveals that subclass-specific chromatin accessibility is significantly correlated with gene expression, providing a resource for generating new specific genetic drivers and revealing regions of the genome that are particularly susceptible to harmful genetic mutations by virtue of their correlation with important developmental genes.