UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis

Vlachogiannis, G; Niederhuth, CE; Tuna, S; Stathopoulou, A; Viiri, K; de Rooij, DG; Jenner, RG; ... Ooi, SK; + view all (2015) The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis. Cell Rep , 10 (6) pp. 944-956. 10.1016/j.celrep.2015.01.021. Green open access

[img]
Preview
Text
1-s2.0-S2211124715000340-main.pdf

Download (4MB) | Preview

Abstract

A critical aspect of mammalian gametogenesis is the reprogramming of genomic DNA methylation. The catalytically inactive adaptor Dnmt3L is essential to ensuring this occurs correctly, but the mechanism by which it functions is unclear. Using gene targeting to engineer a single-amino-acid mutation, we show that the Dnmt3L histone H3 binding domain (ADD) is necessary for spermatogenesis. Genome-wide single-base-resolution DNA methylome analysis of mutant germ cells revealed overall reductions in CG methylation at repetitive sequences and non-promoter CpG islands. Strikingly, we also observe an even more severe loss of non-CG methylation, suggesting an unexpected role for the ADD in this process. These epigenetic deficiencies were coupled with defects in spermatogonia, with mutant cells displaying marked changes in gene expression and reactivation of retrotransposons. Our results demonstrate that the Dnmt3L ADD is necessary for Dnmt3L function and full reproductive fitness.

Type: Article
Title: The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2015.01.021
Publisher version: http://dx.doi.org/10.1016/j.celrep.2015.01.021
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1464095
Downloads since deposit
97Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item