Stem Cell Commons

Promoting Discovery and Reproducibility in Stem Cell Research

User Top Menu

Search experiments

Title: 
ZNF335 regulates stem cell proliferation and neuronal differentiation via Trithorax complex and REST/NRSF [ChIP-Seq]
Measurement Type: 
Transcription Factor Binding (ChIP-Seq)
Factors: 
Immunoprecipitation Antibody
Summary: 
The progression from stem cell to differentiated neuron is associated with extensive chromatin remodeling that controls gene expression, but the mechanisms that connect chromatin to gene expression are not well defined. Here we show that mutation of ZNF335 causes severe human microcephaly ("small brain"), small somatic size, and neonatal death. Germline Znf335 null mutations are embryonically lethal in mice, whereas RNA-interference studies and postmortem human studies show that Znf335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. Znf335 is a component of a vertebrate-specific, trithorax H3K4 methylation complex, while global ChIP-seq and mRNA expression studies show that Znf335 is a previously unsuspected, direct regulator of REST/NRSF, a master regulator of neural gene expression and neural cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF, and provide the first direct evidence that this pathway regulates human neurogenesis and neuronal differentiation. Examination of Znf335-bound genes with two separate antisera.
Contact(s): 
Curator(s): 
mmerrill

Group

Citations: 
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
Yang YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD, Gonzalez DM, Wang EP, Marshall-Walker CA, Barry BJ, Murn J, et al.
Cell. 2012 Nov 21; 151(5):1097-112. PMID: 23178126. Abstract
Download: 
Study metadata (ISA-Tab: isa_15779_747143.zip)