Current studentsExisting staffContact us
 

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

Simple item page
dc.contributor.authorZamudio, N.
dc.contributor.authorScott, H.
dc.contributor.authorWolski, K.
dc.contributor.authorLo, C.
dc.contributor.authorLaw, C.
dc.contributor.authorLeong, D.
dc.contributor.authorKinkel, S.
dc.contributor.authorChong, S.
dc.contributor.authorJolley, D.
dc.contributor.authorSmyth, G.
dc.contributor.authorDe Kretser, D.
dc.contributor.authorWhitelaw, E.
dc.contributor.authorO'Bryan, M.
dc.contributor.editorPera, M.
dc.date.issued2011
dc.descriptionExtent: 12p.
dc.description.abstractPrevious 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.
dc.description.statementofresponsibilityNatasha 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
dc.identifier.citationPLoS One, 2011; 6(3):1-12
dc.identifier.doi10.1371/journal.pone.0018276
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.orcidScott, H. [0000-0002-5813-631X]
dc.identifier.orcidO'Bryan, M. [0000-0001-7298-4940]
dc.identifier.urihttp://hdl.handle.net/2440/71053
dc.language.isoen
dc.publisherPublic Library of Science
dc.rightsCopyright: © 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.
dc.source.urihttps://doi.org/10.1371/journal.pone.0018276
dc.subjectGerm Cells
dc.subjectSpermatozoa
dc.subjectSpermatids
dc.subjectCells, Cultured
dc.subjectX Chromosome
dc.subjectY Chromosome
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectMice
dc.subjectBlotting, Western
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectImmunohistochemistry
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectPolymerase Chain Reaction
dc.subjectMeiosis
dc.subjectTranscription, Genetic
dc.subjectHeterozygote
dc.subjectAlleles
dc.subjectFemale
dc.subjectMale
dc.subjectDNA (Cytosine-5-)-Methyltransferases
dc.titleDNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription
dc.typeJournal article
pubs.publication-statusPublished

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
hdl_71053.pdf
Size:
628.62 KB
Format:
Adobe Portable Document Format
Description:
Published version
Download

Collections

Molecular and Biomedical Science publications