Cited by 156Protein Degradation and InhibitorsDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

Double bromodomain‐containing gene Brd2 is essential for embryonic development in mouse

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Shang, Enyuan, Wang, Xiangyuan, Wen, Duancheng, Greenberg, David A., Wolgemuth, Debra J.·2009·Developmental Dynamics

Abstract

The BET subfamily of bromodomain‐containing genes is characterized by the presence of two bromodomains and a unique ET domain at their carboxyl termini. Here, we show that the founding member of this subfamily, Brd2, is an essential gene by generating a mutant mouse line lacking Brd2 function. Homozygous Brd2 mutants are embryonic lethal, with most Brd2−/− embryos dying by embryonic day 11.5. Before death, the homozygous embryos were notably smaller and exhibited abnormalities in the neural tube where the gene is highly expressed. Brd2‐deficient embryonic fibroblast cells were observed to proliferate more slowly than controls. Experiments to explore whether placental insufficiency could be a cause of the embryonic lethality showed that injecting diploid mutant embryonic stem cells into tetraploid wild‐type blastocysts did not rescue the lethality; that is Brd2‐deficient embryos could not be rescued by wild‐type extraembryonic tissues. Furthermore, there were enhanced levels of cell death in Brd2‐deficient embryos. Developmental Dynamics 238:908–917, 2009. © 2009 Wiley‐Liss, Inc.

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Authors
Shang, E., Wang, X., Wen, D., Greenberg, D. A., & Wolgemuth, D. J.
Affiliations
  • Columbia University Irving Medical Center (US)
  • Rockefeller University (US)
Corresponding author
Wolgemuth, Debra J.
Venue
Developmental Dynamics
Publisher
Wiley
Published
2009-03-19
Volume
238
Issue
4
Pages
908-917
ISSN
  • 1058-8388 (ISSN-L)
  • 1097-0177
OpenAlex
W1983619854
Cited by
156
References
68
Citations by year
2026: 3 · 2025: 9 · 2024: 6 · 2023: 5 · 2022: 13 · 2021: 10 · 2020: 11 · 2019: 12 · 2018: 8 · 2017: 10 · 2016: 14 · 2015: 10 · 2014: 13 · 2013: 8 · 2012: 9
FWCI
3.22
Type
journal article
Language
en
Open access
Locations
  • Developmental Dynamics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM081767, GM081767)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-31775, R01DK031775, T32 DK07647, T32DK007647)
  • National Institute of Neurological Disorders and Stroke (R01NS027941, NS-27941)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
BRD2, BET proteins, embryonic lethality, neural tube defects, placental insufficiency, cell proliferation, cell death, extraembryonic tissues, gene essentiality
MeSH terms
Bromodomain Containing Proteins, Animals, Brain, Cell Line, Chromosomal Proteins, Non-Histone, Embryo, Mammalian, Female, Fibroblasts, Mutation, Phenotype, Placenta, Transcription Factors, Cell Death, Protein Serine-Threonine Kinases, Mice, Knockout, Gene Expression Regulation, Developmental, Embryo Loss, Cell Proliferation, Mice

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