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dc.contributor.authorHwang, Inah
dc.contributor.authorPan, Heng
dc.contributor.authorYao, Jun
dc.contributor.authorElemento, Olivier
dc.contributor.authorZheng, Hongwu
dc.contributor.authorPaik, Jihye
dc.date.accessioned2020-05-06T19:55:47Z
dc.date.available2021-05-06T06:00:29Z
dc.date.issued2020-03
dc.identifier.other32229723
dc.identifier.urihttps://hdl.handle.net/1813/69885
dc.description.abstractCapicua (CIC), a member of the high mobility group (HMG)-box superfamily of transcriptional repressors, is frequently mutated in human oligodendrogliomas. But its function in brain development and tumorigenesis remains poorly understood. Here, we report that brain-specific deletion of Cic compromises developmental transition of neuroblast to immature neurons in mouse hippocampus and compromises normal neuronal differentiation. Combined gene expression and ChIP-seq analyses identified VGF as an important CIC-repressed transcriptional surrogate involved in neuronal lineage regulation. Aberrant VGF expression promotes neural progenitor cell proliferation by suppressing their differentiation. Mechanistically, we demonstrated that CIC represses VGF expression by tethering SIN3-HDAC to form a transcriptional corepressor complex. Mass spectrometry analysis of CIC-interacting proteins further identified BRG1 containing mSWI/SNF complex whose function is necessary for transcriptional repression by CIC. Together, this study uncovers a novel regulatory pathway of CIC-dependent neuronal differentiation and may implicate these molecular mechanisms in CIC-dependent brain tumorigenesis.en_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCapicuaen_US
dc.subjectgene expressionen_US
dc.titleCIC is a Critical Regulator of Neuronal Differentiationen_US
dc.typearticleen_US
dc.relation.doihttps://doi.org/10.1172/jci.insight.135826en_US
dc.identifier.pmid32229723


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