DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription

Zamudio, Natasha M., Scott, Hamish S., Wolski, Katja, Lo, Chi-Yi, Law, Charity, Leong, Dillon, Kinkel, Sarah A., Chong, Suyinn, Jolley, Damien, Smyth, Gordon K., de Kretser, David, Whitelaw, Emma and O'Bryan, Moira K. (2011) DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription. PLoS ONE, 6 3: . doi:10.1371/journal.pone.0018276

Author Zamudio, Natasha M.
Scott, Hamish S.
Wolski, Katja
Lo, Chi-Yi
Law, Charity
Leong, Dillon
Kinkel, Sarah A.
Chong, Suyinn
Jolley, Damien
Smyth, Gordon K.
de Kretser, David
Whitelaw, Emma
O'Bryan, Moira K.
Title DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-03-01
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pone.0018276
Open Access Status DOI
Volume 6
Issue 3
Total pages 12
Place of publication San Francisco United States
Publisher Public Library of Science (PLoS)
Language eng
Formatted 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 auto-regulatory 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 non-coding 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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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