Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 425, Issue 4, Pages 762-768Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.07.149
Keywords
Transgene insertional mutation; Cell cycle exit; Neuronal differentiation; Bromodomain; Brd2; E2F1
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- NCNP [24-12]
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [23390081, 24591618] Funding Source: KAKEN
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To understand genetic programs controlling mammalian central nervous system (CNS) development, we have identified one transgene-inserted mutation, which showed embryonic lethality during neurulation. Determination of the transgene integration site and rescue experiments revealed that the Brd2 gene, whose products specifically bind acetylated histone H4 and can mediate transcription, was the cause of this mutation. Expression studies with specific markers demonstrated that cell cycle progression was accelerated and neuronal differentiation as well as cell cycle exit were impaired in Brd2-deficient neruoepithelial cells. To investigate whether Brd2 regulates neuronal differentiation through a E2F1 transcriptional factor, which directly binds Brd2 and controls genes expression for cell cycle progression and exit, we analyzed Brd2;E2F1 double mutant phenotypes and, consequently found that abnormalities in neuronal differentiation and cell cycle progression due to Brd2-deficiency were restored by removing the E2F1 gene. These findings suggest that Brd2 is required for cell cycle exit and neuronal differentiation of neuroepithelial cells through the E2F1 pathway during mouse CNS development. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.
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