Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells.

Abstract:

:Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.

journal_name

Genome Res

journal_title

Genome research

authors

Hagey DW,Zaouter C,Combeau G,Lendahl MA,Andersson O,Huss M,Muhr J

doi

10.1101/gr.203513.115

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

908-17

issue

7

eissn

1088-9051

issn

1549-5469

pii

gr.203513.115

journal_volume

26

pub_type

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