ZFIN ID: ZDB-PUB-160520-1
Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells
Hagey, D.W., Zaouter, C., Combeau, G., Andersson Lendahl, M., Andersson, O., Huss, M., Muhr, J.
Date: 2016
Source: Genome research   26(7): 908-17 (Journal)
Registered Authors: Lendahl, Monika Andersson
Keywords: none
MeSH Terms:
  • Animals
  • Cells, Cultured
  • Cerebral Cortex/cytology
  • Chromatin/metabolism*
  • Gene Expression
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins/metabolism
  • LIM-Homeodomain Proteins/metabolism
  • Mice
  • Neural Stem Cells/physiology*
  • Protein Binding
  • SOXB1 Transcription Factors/metabolism
  • Spinal Cord/cytology
  • Transcription Factors/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 27197220 Full text @ Genome Res.
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.