Geminin regulates neuronal differentiation by antagonizing Brg1 activity

Seongjin Seo; Anabel Herr; Jong-Won Lim; Genova A Richardson; Helena Richardson; Kristen L Kroll

doi:10.1101/gad.1319105

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Geminin regulates neuronal differentiation by antagonizing Brg1 activity

Journal article

Open access

Peer reviewed

Geminin regulates neuronal differentiation by antagonizing Brg1 activity

Seongjin Seo, Anabel Herr, Jong-Won Lim, Genova A Richardson, Helena Richardson and Kristen L Kroll

Genes & development, Vol.19(14), pp.1723-1734

07/15/2005

DOI: 10.1101/gad.1319105

PMCID: PMC1176010

PMID: 16024661

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Abstract

Precise control of cell proliferation and differentiation is critical for organogenesis. Geminin (Gem) has been proposed to link cell cycle exit and differentiation as a prodifferentiation factor and plays a role in neural cell fate acquisition. Here, we identified the SWI/SNF chromatin-remodeling protein Brg1 as an interacting partner of Gem. Brg1 has been implicated in cell cycle withdrawal and cellular differentiation. Surprisingly, we discovered that Gem antagonizes Brg1 activity during neurogenesis to maintain the undifferentiated cell state. Down-regulation of Gem expression normally precedes neuronal differentiation, and gain- and loss-of-function experiments in Xenopus embryos and mouse P19 cells demonstrated that Gem was essential to prevent premature neurogenesis. Misexpression of Gem also suppressed ectopic neurogenesis driven by Ngn and NeuroD. Gem's activity to block differentiation depended upon its ability to bind Brg1 and could be mediated by Gem's inhibition of proneural basic helix-loop-helix (bHLH)-Brg1 interactions required for bHLH target gene activation. Our data demonstrate a novel mechanism of Gem activity, through regulation of SWI/SNF chromatin-remodeling proteins, and indicate that Gem is an essential regulator of neurogenesis that can control the timing of neural progenitor differentiation and maintain the undifferentiated cell state.

Xenopus

Monomeric GTP-Binding Proteins - physiology

Xenopus Proteins - genetics

Humans

Nervous System - metabolism

Transcriptional Activation

Neurons - cytology

Gene Expression Profiling

Xenopus Proteins - chemistry

Cell Cycle Proteins - chemistry

Drosophila Proteins - physiology

Gene Expression Regulation, Developmental

Base Sequence

Immediate-Early Proteins - chemistry

Cell Cycle Proteins - genetics

Drosophila - embryology

Cell Differentiation

Neurons - metabolism

Geminin

Nervous System - embryology

Binding Sites

Drosophila - genetics

Cell Line

Immediate-Early Proteins - physiology

Drosophila - cytology

Transcription Factors - antagonists & inhibitors

Monomeric GTP-Binding Proteins - genetics

DNA - genetics

DNA Helicases

Animals

Immediate-Early Proteins - genetics

Mutagenesis

Monomeric GTP-Binding Proteins - chemistry

Nuclear Proteins - antagonists & inhibitors

Xenopus Proteins - physiology

Mice

Drosophila - metabolism

Drosophila Proteins - genetics

HeLa Cells

Models, Neurological

Cell Cycle Proteins - physiology

Details

Title: Subtitle: Geminin regulates neuronal differentiation by antagonizing Brg1 activity
Creators: Seongjin Seo - Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
Anabel Herr
Jong-Won Lim
Genova A Richardson
Helena Richardson
Kristen L Kroll
Resource Type: Journal article
Publication Details: Genes & development, Vol.19(14), pp.1723-1734
Publisher: United States
DOI: 10.1101/gad.1319105
PMID: 16024661
PMCID: PMC1176010
ISSN: 0890-9369
eISSN: 1549-5477
Grant note: GM66815-1 / NIGMS NIH HHS R01 GM066815 / NIGMS NIH HHS
Language: English
Date published: 07/15/2005
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980388802771

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