PubMed:23178126 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/23178126","sourcedb":"PubMed","sourceid":"23178126","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/23178126","text":"Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.\nMicrocephaly 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 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