|An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse. |
Daxinger, L; Harten, SK; Oey, H; Epp, T; Isbel, L; Huang, E; Whitelaw, N; Apedaile, A; Sorolla, A; Yong, J; Bharti, V; Sutton, J; Ashe, A; Pang, Z; Wallace, N; Gerhardt, DJ; Blewitt, ME; Jeddeloh, JA; Whitelaw, E
We have used a sensitized ENU mutagenesis screen to produce mouse lines that carry mutations in genes required for epigenetic regulation. We call these lines Modifiers of murine metastable epialleles (Mommes).We report a basic molecular and phenotypic characterization for twenty of the Momme mouse lines, and in each case we also identify the causative mutation. Three of the lines carry a mutation in a novel epigenetic modifier, Rearranged L-myc fusion (Rlf), and one gene, Rap-interacting factor 1 (Rif1), has not previously been reported to be involved in transcriptional regulation in mammals. Many of the other lines are novel alleles of known epigenetic regulators. For two genes, Rlf and Widely-interspaced zinc finger (Wiz), we describe the first mouse mutants. All of the Momme mutants show some degree of homozygous embryonic lethality, emphasizing the importance of epigenetic processes. The penetrance of lethality is incomplete in a number of cases. Similarly ,abnormalities in phenotype seen in the heterozygous individuals of some lines occur with incomplete penetrance.Recent advances in sequencing enhance the power of sensitized mutagenesis screens to identify the function of previously uncharacterized factors and to discover additional functions for previously characterized proteins. The observation of incomplete penetrance of phenotypes in these inbred mutant mice, at various stages of development, is of interest. Overall, the Momme collection of mouse mutants provides a valuable resource for researchers across many disciplines.
|E2F6 associates with BRG1 in transcriptional regulation. |
Leung, JY; Nevins, JR
The E2F6 protein functions as an Rb-independent repressor of gene transcription. We have previously provided evidence suggesting a role for E2F6 in repression of E2F-responsive genes at S phase. Here, we have identified BRG1, the ATPase subunit of the SWI/SNF chromatin-remodeling complex, as an E2F6 interacting protein. Immunoprecipitation experiments demonstrate that BRG1 binds specifically to E2F6 and E2F4 but not the activator E2Fs. E2F6 was also able to interact with BAF155, a BRG1-associated factor, in the SWI/SNF complex. Chromatin immunoprecipitation assays demonstrate the binding of BRG1 coincident with E2F6 on G1/S gene promoters during S phase. Collectively, our studies suggest that E2F6 may recruit BRG1 in transcriptional regulation of genes important for G1/S phase transition of the cell cycle.