PMID- 34150772 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210622 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 9 DP - 2021 TI - Histone Arginine Methyltransferase CARM1-Mediated H3R26me2 Is Essential for Morula-to-Blastocyst Transition in Pigs. PG - 678282 LID - 10.3389/fcell.2021.678282 [doi] LID - 678282 AB - Coactivator-associated arginine methyltransferase 1 (CARM1) is involved in both establishment of first pluripotent lineage and pluripotency maintenance of embryonic stem cells (ESCs) in mice. However, the histone substrates and role of CARM1 in early embryonic development remain largely unknown. Here, we show that CARM1 specifically catalyzes H3R26me2 to promote porcine blastocyst formation. The putative histone substrates of CARM1, including H3R2me2, H3R17me2, and H3R26me2, are present in pig early embryos. The changes of CARM1 mRNA during early embryogenesis parallel that of H3R26me2. Functional studies using a combinational approach of chemical inhibition and RNA interference (RNAi) showed that catalytic activity inhibition of CARM1 protein or knockdown (KD) of CARM1 mRNA did not alter the levels of both H3R2me2 and H3R17me2, but significantly reduced H3R26me2 levels in porcine embryos. Furthermore, CARM1 inhibition or KD did not affect embryo development to the 2-cell, 4-cell, 8-cell, and morula stages, but severely compromised blastocyst development. CARM1 knocked down embryos that developed to the blastocyst stage had fewer total cells, inner cell mass (ICM), and trophectoderm (TE) cells. Mechanistically, single embryo RNA-sequencing analysis revealed that CARM1 KD altered the transcriptome characterized by downregulation of key genes associated with Hippo and PI3K-AKT signaling pathways. Taken together, these results demonstrate that CARM1 specifically catalyzes H3R26me2 in porcine embryos and participates in blastocyst development. CI - Copyright (c) 2021 Cao, Tong, Yin, Zhou, Zhang, Zhang, Wang, Liu, Yan, Ma, Yu, Li and Zhang. FAU - Cao, Zubing AU - Cao Z AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Tong, Xu AU - Tong X AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Yin, Huiqun AU - Yin H AD - Reproductive Medicine Center, The 901st Hospital, Hefei, China. FAU - Zhou, Naru AU - Zhou N AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. AD - Reproductive and Genetic Branch, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Zhang, Xiangdong AU - Zhang X AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Zhang, Mengya AU - Zhang M AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Wang, Xin AU - Wang X AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Liu, Qiuchen AU - Liu Q AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Yan, Yelian AU - Yan Y AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Ma, Yangyang AU - Ma Y AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Yu, Tong AU - Yu T AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Li, Yunsheng AU - Li Y AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. FAU - Zhang, Yunhai AU - Zhang Y AD - Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China. LA - eng PT - Journal Article DEP - 20210602 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC8206646 OTO - NOTNLM OT - CARM1 OT - H3R26me2 OT - blastocyst OT - lineage specification OT - pig COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/06/22 06:00 MHDA- 2021/06/22 06:01 PMCR- 2021/01/01 CRDT- 2021/06/21 06:01 PHST- 2021/03/09 00:00 [received] PHST- 2021/05/10 00:00 [accepted] PHST- 2021/06/21 06:01 [entrez] PHST- 2021/06/22 06:00 [pubmed] PHST- 2021/06/22 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2021.678282 [doi] PST - epublish SO - Front Cell Dev Biol. 2021 Jun 2;9:678282. doi: 10.3389/fcell.2021.678282. eCollection 2021.