alexa Microcephaly gene links trithorax and REST NRSF to control neural stem cell proliferation and differentiation.
Genetics

Genetics

Single Cell Biology

Author(s): Yang YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD, , Yang YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD,

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Abstract Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation. Here, we identify and characterize a nuclear zinc finger protein, ZNF335/NIF-1, as a causative gene for severe microcephaly, small somatic size, and neonatal death. Znf335 null mice are embryonically lethal, and conditional knockout leads to severely reduced cortical size. RNA-interference 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, directly regulating REST/NRSF, a master regulator of neural gene expression and 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 genetic evidence that this pathway regulates human neurogenesis and neuronal differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.
This article was published in Cell and referenced in Single Cell Biology

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