Loss of maternal Trim28 causes male-predominant early embryonic lethality

Abhishek Sampath Kumar; Michelle K.Y. Seah; Ka Yi Ling; Yaju Wang; Joel H.L. Tan; Sandra Nitsch; Shu Ly Lim; Chanchao Lorthongpanich; Heike Wollmann; Diana H.P. Low; Ernesto Guccione; Daniel M. Messerschmidt

doi:10.1101/gad.291195.116

Loss of maternal Trim28 causes male-predominant early embryonic lethality

Abhishek Sampath Kumar, Michelle K.Y. Seah, Ka Yi Ling, Yaju Wang, Joel H.L. Tan, Sandra Nitsch, Shu Ly Lim, Chanchao Lorthongpanich, Heike Wollmann, Diana H.P. Low, Ernesto Guccione, Daniel M. Messerschmidt

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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.

Original language	English
Pages (from-to)	12-17
Number of pages	6
Journal	Genes and Development
Volume	31
Issue number	1
DOIs	https://doi.org/10.1101/gad.291195.116
State	Published - 1 Jan 2017
Externally published	Yes

Keywords

DNA methylation
Epigenetics
Rbmy
Reprogramming
Splicing
Trim28

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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.",

keywords = "DNA methylation, Epigenetics, Rbmy, Reprogramming, Splicing, Trim28",

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doi = "10.1101/gad.291195.116",

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AU - Kumar, Abhishek Sampath

AU - Seah, Michelle K.Y.

AU - Ling, Ka Yi

AU - Wang, Yaju

AU - Tan, Joel H.L.

AU - Nitsch, Sandra

AU - Lim, Shu Ly

AU - Lorthongpanich, Chanchao

AU - Wollmann, Heike

AU - Low, Diana H.P.

AU - Guccione, Ernesto

AU - Messerschmidt, Daniel M.

PY - 2017/1/1

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N2 - 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.

AB - 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.

KW - DNA methylation

KW - Epigenetics

KW - Rbmy

KW - Reprogramming

KW - Splicing

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Loss of maternal Trim28 causes male-predominant early embryonic lethality

Abstract

Keywords

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