title: Loss of maternal Trim28 causes male-predominant early embryonic lethality.
abstract: Global DNA demethylation is a hallmark of embryonic epigenetic reprogramming. However, embryos engage noncanonical DNA methylation maintenance mechanisms to ensure inheritance of exceptional epigenetic germline features to the soma. Besides the paradigmatic genomic imprints, these exceptions remain ill-defined, and the mechanisms ensuring demethylation resistance in the light of global reprogramming remain poorly understood. Here we show that the Y-linked gene Rbmy1a1 is highly methylated in mature sperm and resists DNA demethylation post-fertilization. Aberrant hypomethylation of the Rbmy1a1 promoter results in its ectopic activation, causing male-specific peri-implantation lethality. Rbmy1a1 is a novel target of the TRIM28 complex, which is required to protect its repressive epigenetic state during embryonic epigenetic reprogramming.
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Sampath Kumar
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.
authors.forename: Michelle K Y
authors.initials: MK
authors.lastname: Seah
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.
authors.forename: Ka Yi
authors.initials: KY
authors.lastname: Ling
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.
authors.forename: Yaju
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074.
authors.forename: Joel H L
authors.initials: JH
authors.lastname: Tan
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nitsch
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.
authors.forename: Shu Ly
authors.initials: SL
authors.lastname: Lim
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Chanchao
authors.initials: C
authors.lastname: Lorthongpanich
authors.affiliation: Next-Generation Sequencing Unit of DNA Sequencing Facility, IMCB, A*STAR, 138673, Singapore.
authors.forename: Heike
authors.initials: H
authors.lastname: Wollmann
authors.affiliation: Methyltransferases in Development and Disease Group, IMCB, A*STAR, Singapore 138673.
authors.forename: Diana H P
authors.initials: DH
authors.lastname: Low
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074.|Methyltransferases in Development and Disease Group, IMCB, A*STAR, Singapore 138673.
authors.forename: Ernesto
authors.identifier: 0000-0001-7764-5307
authors.initials: E
authors.lastname: Guccione
authors.affiliation: Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), Singapore 138673.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Messerschmidt
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D010064:Embryo Implantation / Q000235:genetics; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C501500:Rbmy protein, mouse; D012097:Repressor Proteins; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28
keywords: DNA methylation; Rbmy; Trim28; epigenetics; reprogramming; splicing