Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/71053
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Type: Journal article
Title: DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription
Author: Zamudio, N.
Scott, H.
Wolski, K.
Lo, C.
Law, C.
Leong, D.
Kinkel, S.
Chong, S.
Jolley, D.
Smyth, G.
De Kretser, D.
Whitelaw, E.
O'Bryan, M.
Citation: PLoS One, 2011; 6(3):1-12
Publisher: Public Library of Science
Issue Date: 2011
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Natasha M. Zamudio, Hamish S. Scott, Katja Wolski, Chi-Yi Lo, Charity Law, Dillon Leong, Sarah A. Kinkel, Suyinn Chong, Damien Jolley, Gordon K. Smyth, David de Kretser, Emma Whitelaw and Moira K. O’Bryan
Abstract: Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L), have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e., wild type offspring of heterozygous mutant sires display abnormal phenotypes suggesting the inheritance of aberrant epigenetic marks on the paternal chromosomes. In order to reveal the mechanisms underlying these paternal effects, we have assessed X chromosome meiotic compaction, XY chromosome aneuploidy rates and global transcription in meiotic and haploid germ cells from male mice heterozygous for Dnmt3L. XY bodies from Dnmt3L heterozygous males were significantly longer than those from wild types, and were associated with a three-fold increase in XY bearing sperm. Loss of a Dnmt3L allele resulted in deregulated expression of a large number of both X-linked and autosomal genes within meiotic cells, but more prominently in haploid germ cells. Data demonstrate that similar to embryonic stem cells, DNMT3L is involved in an autoregulatory loop in germ cells wherein the loss of a Dnmt3L allele resulted in increased transcription from the remaining wild type allele. In contrast, however, within round spermatids, this auto-regulatory loop incorporated the alternative noncoding alternative transcripts. Consistent with the mRNA data, we have localized DNMT3L within spermatids and sperm and shown that the loss of a Dnmt3L allele results in a decreased DNMT3L content within sperm. These data demonstrate previously unrecognised roles for DNMT3L in late meiosis and in the transcriptional regulation of meiotic and post-meiotic germ cells. These data provide a potential mechanism for some cases of human Klinefelter’s and Turner’s syndromes.
Keywords: Germ Cells; Spermatozoa; Spermatids; Cells, Cultured; X Chromosome; Y Chromosome; Animals; Mice, Knockout; Mice; DNA (Cytosine-5-)-Methyltransferase; Blotting, Western; Oligonucleotide Array Sequence Analysis; Immunohistochemistry; In Situ Hybridization, Fluorescence; Polymerase Chain Reaction; Meiosis; Transcription, Genetic; Heterozygote; Alleles; Female; Male
Description: Extent: 12p.
Rights: Copyright: © 2011 Zamudio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020105672
DOI: 10.1371/journal.pone.0018276
Appears in Collections:Molecular and Biomedical Science publications

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