Abstract
Peg3 (paternally expressed gene 3) encodes a DNA-binding protein that functions as a transcriptional repressor. Recent studies revealed that PEG3 binds to Msl1 (male-specific lethal 1) and Msl3, the two main components of the MSL complex. In the current study, we investigated potential roles of Peg3 in controlling its downstream genes through H4K16ac, the histone modification by the MSL complex. According to the results, complete removal of PEG3 resulted in up-regulation of Msl1 and Msl3, and subsequently an increase in the global levels of H4K16ac, confirming PEG3 as a transcriptional repressor for MSL during mammalian development. Genome-wide analyses further revealed that about 10% of the entire gene catalogue was affected in the MEF cells lacking PEG3, displaying the increased levels of H4K16ac in their promoter regions. The expression levels of a small subset of the affected genes were up-regulated in the MEF cells lacking PEG3. Interestingly, three Hox clusters also exhibited changes in the levels of H4K16ac, suggesting potential roles of PEG3 and MSL in the regulation of Hox clusters. Overall, the current study reports that Peg3 may control its downstream genes through mammalian MSL.
Highlights
Peg3 is an imprinted gene that is localized in the human chromosome 19q13.4/ proximal mouse chromosome 7 [1]
Potential binding of PEG3 to Msl1 and Msl3 was initially observed from Chromatin ImmunoPrecipitation (ChIP)-seq studies using a set of Mouse Embryonic Fibroblast (MEF) cells that had been derived from the 14.5-dpc embryos of the crossing between male Peg3CoKO/+ and female littermates [14]
The chromatin prepared from WT and KO MEFs were immunoprecipitated with a commercial antibody against PEG3, and subsequently analyzed using a high throughput sequencing protocol [14]
Summary
Peg (paternally expressed gene 3) is an imprinted gene that is localized in the human chromosome 19q13.4/ proximal mouse chromosome 7 [1]. This gene is a founding member of the 500-kb evolutionarily conserved domain, containing 6 additional imprinted genes [2]. The maternal allele of Peg is inactive and only the paternal allele is functional throughout the lifetime of mammals [5]. Genome-wide expression analyses revealed that many genes are up-regulated in the mutant mice targeting Peg, including several placenta-specific gene families and a subset of genes that are involved in fatty acid metabolism [7].
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