Activation and demethylation of the intracisternal A particle genes by 5-azacytidine

Davis, Caroline; Constantinides, Phillip G.; Gevers, Wieland; Parker, M. Iqbal; Riet, F. Van Der; Schalkwyk, Lynette van

doi:10.1016/0922-3371(89)90738-7

Cited by 13 publications

(11 citation statements)

References 27 publications

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“…The role of DNA methylation in transposon silencing is well established and it has been shown earlier that loss of DNA methylation in somatic cells correlates with VL30, IAP and MuLV expression [37]–[39]. Indeed, Aza-dC treatment in fibroblasts caused highly elevated VL30, IAP and MuLV mRNA levels, but had no effect on other TEs tested (Figure 3, lower panel and Figure S1).…”

Section: Resultsmentioning

confidence: 75%

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

et al. 2010

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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.

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Section: Resultsmentioning

confidence: 75%

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

et al. 2010

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“…Thus, the germline-specific expression of IAP elements does not appear to be caused by germ cell-specific transcription factors. Rather, the preferential expression of IAP elements in the germline appears to be a consequence of IAP element DNA being hypomethylated in germ cells, but methylated and silenced in somatic cells [42–45]. Within the germline, IAP LTR-driven expression of a LacZ reporter is restricted to a fairly small window of germ cell development, with activity detectable in quiescent male foetal germ cells from E16, and in undifferentiated spermatogonia in adult testes [40].…”

Section: Retrotransposon Expression In Germ Cells and Pluripotent Cellsmentioning

confidence: 99%

“…Experimentally removing DNA methylation in mouse somatic tissues strongly induces expression of IAP retrotransposons, suggesting that DNA methylation has a primary role in repressing these elements in mouse embryonic fibroblasts [42–44]. It is not clear how many other retrotransposons rely predominantly on DNA methylation for their repression in somatic tissues.…”

Section: Epigenetic Silencing Of Retrotransposons By Dna Methylationmentioning

confidence: 99%

“…Although a number of studies have reported that loss of DNA methylation causes strong upregulation of IAP elements in somatic tissues, ES cells carrying mutations in all three DNA methyltransferases exhibit a more modest upregulation of these elements, even though IAP DNA methylation is severely reduced [42–45, 125, 128–130]. Therefore, DNA methylation does not play as dominant a role in IAP suppression in ES cells as it does in somatic cells.…”

Section: Transcriptional Silencing Of Retrotransposon Expression In Ementioning

confidence: 99%

“…Notably, DNA methylation at IAP elements is not strongly affected in Trim28 − / − ES cells [136, 140], suggesting that TRIM28 is silencing retrotransposons independently of DNA methylation in this cell type. Interestingly, the primary transcriptional silencing mechanism for IAP retrotransposons appears to switch from being TRIM28/SETDB1-dependent histone modification in ES cells to DNA methylation in somatic cells [42, 43, 45, 128, 129, 132, 136]. Recent findings that differentiation of pluripotent Trim28 − / − cells into somatic cells results in some reduction in the amount of DNA methylation at IAP retrotransposons suggests that there is a temporal link between TRIM28 and DNA methylation during differentiation and development [140].…”

Section: Transcriptional Silencing Of Retrotransposon Expression In Ementioning

confidence: 99%

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Defending the genome from the enemy within: mechanisms of retrotransposon suppression in the mouse germline

Crichton

Dunican

MacLennan

et al. 2013

Cell. Mol. Life Sci.

112

117

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The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline.

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Elevation of large‐T antigen production by sodium butyrate treatment of SV40‐transformed WI‐38 fibroblasts

1992

J of Cellular Biochemistry

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The effects of sodium butyrate on simian virus 40 early gene expression were determined in SV40-transformed human embryonic lung fibroblasts (SVWI-38). Northern blot analysis and nuclear run-off transcription studies revealed that treatment of cells with millimolar concentrations of sodium butyrate (2.5 to 10 mM) resulted in increased levels of SV40 early gene transcripts, with a concomitant increase in their corresponding proteins (large-T and small-t antigens). Although sodium butyrate treatment enhanced the expression of the early genes, it was associated with a reduction in cell growth and total protein synthesis, as measured by cell number and incorporation of 3H-leucine into macromolecules, respectively. Immunoprecipitation of 35S-labelled cellular proteins with anti-p53 and anti-T antibodies revealed that the level of the cellular protein, p53, declined markedly in the presence of sodium butyrate. Furthermore, in control cells only 30% of the p53 was complexed with large-T antigen, whereas in butyrate-treated cells all the p53 was complexed with large-T antigen. The increased early gene expression was not due to altered methylation patterns, gene amplification, or rearrangement of the integrated SV40 genome. Sodium butyrate treatment did, however, result in the appearance of a new nuclear protein which bound specifically to a SV40 promoter fragment containing large-T antigen binding sites I and II.

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Activation and demethylation of the intracisternal A particle genes by 5-azacytidine

Cited by 13 publications

References 27 publications

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

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

Defending the genome from the enemy within: mechanisms of retrotransposon suppression in the mouse germline

Elevation of large‐T antigen production by sodium butyrate treatment of SV40‐transformed WI‐38 fibroblasts

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