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  current news   Press   selected story    
     
  2 February 2017  
 
Loss of maternal Trim28 causes male-predominant early-embryonic lethality 
 
 




Authors
Abhishek Sampath Kumar1, Michelle K. Y. Seah1,*, Ka Yi Ling1,*, Yaju Wang1, Joel H. L. Tan1,2, Sandra Nitsch1, Shu Ly Lim1, Chanchao Lorthongpanich3, Heike Wollmann4, Diana H. P. Low5, Ernesto Guccione2,5, Daniel M. Messerschmidt1,2,#

1  Developmental Epigenetics and Disease Group, Institute of Molecular and Cell Biology (IMCB), Agency    for Science, Technology and Research (A*STAR), 138673, Singapore
2  Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore,    119074, Singapore
3  Siriraj Center of Excellence for Stem Cell Research, Mahidol University, Bangkok, Thailand
4  NGS Unit of DNA Sequencing Facility, IMCB, A*STAR, 138673, Singapore

Published online ahead of print in Genes & Development on 23 January 2017.
Please see http://genesdev.cshlp.org/content/early/2017/01/23/gad.291195.116.full.pdf+html

Abstract
Global DNA demethylation is a hallmark of embryonic epigenetic reprogramming. Yet, embryos engage non-canonical 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 ectopicactivation causing male-specific periimplantation lethality. Rbmy1a1 is a novel target of the TRIM28 complex, which is required to protect its repressive epigenetic state during embryonic epigenetic reprogramming.

Figure

Figure legend

Absence of maternal Trim28 results in the ectopic activation of the Y-chromosomal gene RBMY1A1 (red), which is not found in control male embryos (middle row) or mutant females (distinguished by X-linked GFP expression, bottom row). Ectopic activation of RBMY1A1 results in peri-implantation lethality, which is apparent in the morphological abnormality of mutant male embryos at E4.5 (top row).

For more information on Daniel MESSERCHMIDT's lab, please click here.

For more information on Ernesto GUCCIONE's lab, please click here.