title: Epigenetic disruptions of histone signatures for the trophectoderm and inner cell mass in mouse parthenogenetic embryos.
abstract: Epigenetic asymmetry has been shown to be associated with the first lineage allocation event in preimplantation development, that is, the formation of the trophectoderm (TE) and inner cell mass (ICM) lineages in the blastocyst. Since parthenogenesis causes aberrant segregation between the TE and ICM lineages, we examined several development-associated histone modifications in parthenotes, including those involved in (i) transcriptional activation [acetylated histone H3 lysine 9 (H3K9Ac) and lysine 14 (H3K14Ac), trimethylated histone H3 lysine 4 (H3K4Me3), and dimethylated histone H3 arginine 26 (H3R26Me2)] and (ii) transcriptional repression [trimethylated histone H3 lysine 9 (H3K9Me3) and lysine 27 (H3K27Me3), and mono-ubiquitinated histone H2A lysine 119 (H2AK119u1)]. Here, we report that in parthenotes, H3R26Me2 expression decreased from the morula stage, while expression patterns and levels of H3K9Ac, H3K27Me3, and H2AK119u1 were unchanged until the blastocyst stage; whereas H3K14Ac, H3K4Me3, and H3K9Me3 showed normal patterns and levels of expressions. Relative to the decrease of H3K9Ac in the ICM and increase in the TE of parthenotes, we detected reduced expression of TAT-interactive protein 60 acetyltransferase and histone deacetylase 1 deacetylase in the ICM and TE of parthenotes, respectively. Relative to the decrease of H3R26Me2, we also observed decreased expression of coactivator-associated arginine methyltransferase 1 methyltransferase and increased expression of the Wnt effector transcription factor 7L2 and miR-181c microRNA in parthenotes. Furthermore, relative to the decrease in H3K27Me3 and H2AK119u1, we found increased phosphorylation of Akt1 and enhancer of zeste homolog 2 in parthenogenetic TE. Therefore, our findings that histone signatures are impaired in parthenotes provide a mechanistic explanation for aberrant lineage segregation and TE defects.
authors.affiliation: 1 Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center , Taipei, Taiwan .
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Yu
mesh_terms: D000107:Acetylation; D000818:Animals; D053624:Blastocyst Inner Cell Mass / Q000166:cytology / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D000074443:Lysine Acetyltransferase 5; D008297:Male; D008745:Methylation; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D035683:MicroRNAs / Q000378:metabolism; D010312:Parthenogenesis; D010766:Phosphorylation; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000071221:Enhancer of Zeste Homolog 2 Protein; D051548:Histone Acetyltransferases; D056284:Histone Deacetylase 1; D006657:Histones; D000074443:Lysine Acetyltransferase 5; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; D011484:Protein-Arginine N-Methyltransferases; D051057:Proto-Oncogene Proteins c-akt; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C544895:Tcf7l2 protein, mouse; C529100:mirn181 microRNA, mouse; C119966:coactivator-associated arginine methyltransferase 1; C498410:Ezh2 protein, mouse; C523065:Kat5 protein, mouse; C514862:Akt1 protein, mouse; C484389:Hdac1 protein, mouse