Metastasis tumor antigen 2 (MTA2) is involved in proper imprinted expression of H19 and Peg3 during mouse preimplantation development.
The epigenetic mechanisms involved in establishing and maintaining genomic imprinting are steadily being unmasked. The nucleosome remodeling and histone deacetylation (NuRD) complex is implicated in regulating DNA methylation and expression of the maternally expressed H19 gene in preimplantation mouse embryos. To dissect further the function of the NuRD complex in genomic imprinting, we employed an RNA interference (RNAi) strategy to deplete the NuRD complex component Metastasis Tumor Antigen 2 (MTA2). We found that Mta2 is the only zygotically expressed Mta gene prior to the blastocyst stage, and that RNAi-mediated knockdown of Mta2 transcript leads to biallelic H19 expression and loss of DNA methylation in the differentially methylated region in blastocysts. In addition, biallelic expression of the paternally expressed Peg3 gene, but not Snrpn, is also observed in blastocysts following Mta2 knockdown. Loss of MTA2 protein does not result in a decrease in abundance of other NuRD components, including methyl-binding-CpG-binding domain protein 3 (MBD3), histone deacetylases 1 and 2 (HDACs 1 and 2), and chromodomain helicase DNA-binding protein 4 (CHD4). Taken together, our results support a role for MTA2 within the NuRD complex in genomic imprinting.
Ma
Pengpeng
P
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018, USA.
Lin
Shu
S
Bartolomei
Marisa S
MS
Schultz
Richard M
RM
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D019175:DNA Methylation; D046149:Embryo Culture Techniques; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D017930:Genes, Reporter; D018392:Genomic Imprinting; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009866:Oogenesis; D034622:RNA Interference; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015053:Zygote / Q000166:cytology / Q000378:metabolism
C094335:H19 long non-coding RNA; D051741:Kruppel-Like Transcription Factors; C529798:Mta2 protein, mouse; C097901:Peg3 protein, mouse; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D015534:Trans-Activators; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex