Epigenetic Regulation of a Murine Retrotransposon by a Dual Histone Modification Mark

被引：50

作者：

Brunmeir, Reinhard ^{[1
]}

Lagger, Sabine ^{[1
]}

Simboeck, Elisabeth ^{[1
]}

Sawicka, Anna ^{[1
]}

Egger, Gerda ^{[2
]}

Hagelkruys, Astrid ^{[1
]}

Zhang, Yu ^{[3
]}

Matthias, Patrick ^{[3
]}

Miller, Wolfgang J. ^{[4
]}

Seiser, Christian ^{[1
]}

机构：

[1] Med Univ Vienna, Vienna Bioctr, Max F Perutz Labs, Vienna, Austria

[2] Med Univ Vienna, Dept Clin Pathol, Vienna, Austria

[3] Novartis Res Fdn, Friedrich Miescher Inst Biomed Res, Basel, Switzerland

[4] Med Univ Vienna, Ctr Anat & Cell Biol, Labs Genome Dynam, Vienna, Austria

来源：

PLOS GENETICS | 2010年 / 6卷 / 04期

基金：

英国生物技术与生命科学研究理事会; 奥地利科学基金会;

关键词：

ENDOGENOUS RETROVIRUSES; TRANSPOSABLE ELEMENTS; SACCHAROMYCES-CEREVISIAE; H3; PHOSPHORYLATION; INSERTIONAL MUTAGENESIS; DNA METHYLTRANSFERASE-1; DEACETYLASE INHIBITORS; GENE-EXPRESSION; MOUSE OOCYTES; CANCER-CELLS;

D O I：

10.1371/journal.pgen.1000927

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Large fractions of eukaryotic genomes contain repetitive sequences of which the vast majority is derived from transposable elements (TEs). In order to inactivate those potentially harmful elements, host organisms silence TEs via methylation of transposon DNA and packaging into chromatin associated with repressive histone marks. The contribution of individual histone modifications in this process is not completely resolved. Therefore, we aimed to define the role of reversible histone acetylation, a modification commonly associated with transcriptional activity, in transcriptional regulation of murine TEs. We surveyed histone acetylation patterns and expression levels of ten different murine TEs in mouse fibroblasts with altered histone acetylation levels, which was achieved via chemical HDAC inhibition with trichostatin A (TSA), or genetic inactivation of the major deacetylase HDAC1. We found that one LTR retrotransposon family encompassing virus-like 30S elements (VL30) showed significant histone H3 hyperacetylation and strong transcriptional activation in response to TSA treatment. Analysis of VL30 transcripts revealed that increased VL30 transcription is due to enhanced expression of a limited number of genomic elements, with one locus being particularly responsive to HDAC inhibition. Importantly, transcriptional induction of VL30 was entirely dependent on the activation of MAP kinase pathways, resulting in serine 10 phosphorylation at histone H3. Stimulation of MAP kinase cascades together with HDAC inhibition led to simultaneous phosphorylation and acetylation (phosphoacetylation) of histone H3 at the VL30 regulatory region. The presence of the phosphoacetylation mark at VL30 LTRs was linked with full transcriptional activation of the mobile element. Our data indicate that the activity of different TEs is controlled by distinct chromatin modifications. We show that activation of a specific mobile element is linked to a dual epigenetic mark and propose a model whereby phosphoacetylation of histone H3 is crucial for full transcriptional activation of VL30 elements.

引用

页数：16