Abstract
BackgroundThe NuRD/Mi2 chromatin complex is involved in histone modifications and contains a large number of subunits, including the p66 protein. There are two mouse and human p66 paralogs, p66α and p66β. The functions of these genes are not clear, in part because there are no mutants available, except in invertebrate model systems.MethodologyWe made loss of function mutants in the mouse p66α gene (mp66α, official name Gatad2a, MGI:2384585). We found that mp66α is essential for development, as mutant embryos die around day 10 of embryogenesis. The gene is not required for normal blastocyst development or for implantation. The phenotype of mutant embryos and the pattern of gene expression in mutants are consistent with a role of mp66α in gene silencing.Conclusionmp66α is an essential gene, required for early mouse development. The lethal phenotype supports a role in execution of methylated DNA silencing.
Highlights
Epigenetic changes in gene expression, such as occurring during imprinting and X chromosome inactivation, can result from DNA methylation and from chromatin remodeling
The resulting protein would consist of 86 amino acids from the non-conserved region, followed by 34 amino acids not encoded by the gene and a stop codon well before the CR1 region
The lethal phenotype is consistent with a role in execution of methylated DNA silencing The mp66a2/2 mutation results in an embryonic lethal phenotype at around day e9.5
Summary
Epigenetic changes in gene expression, such as occurring during imprinting and X chromosome inactivation, can result from DNA methylation and from chromatin remodeling. The latter includes histone modifications such as deacetylation [1], acetylation [2], and methylation [3]. Proteins that bind preferentially to methylated DNA have been isolated These include MeCP2, and MBDs 1, 2, and 4 [7,8,9]. The NuRD/Mi2 chromatin complex is involved in histone modifications and contains a large number of subunits, including the p66 protein. Mp66a is an essential gene, required for early mouse development. The lethal phenotype supports a role in execution of methylated DNA silencing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
