Schistosoma mansoni histones: From transcription to chromatin regulation; an in silico analysis

Anderson, Letícia; Pierce, Raymond J.; Verjovski-Almeida, Sérgio

doi:10.1016/j.molbiopara.2012.03.001

Cited by 15 publications

(11 citation statements)

References 55 publications

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“…An in silico analysis of the schistosome genome predictions and EST libraries (Anderson et al, 2012) showed that 21 of the 29 histone genes predicted in the genome are expressed in S. mansoni , the remainder being either unexpressed or having divergent sequences. Importantly, the N-terminal tails of the nucleosomal histones H3 and H4 are highly conserved, suggesting the functional conservation of the histone marks found in mammalian histones.…”

Section: Post-translational Modifications Of Histonesmentioning

confidence: 99%

Epigenetic control of gene function in schistosomes: a source of therapeutic targets?

et al. 2014

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The discovery of the epigenetic regulation of gene expression has revolutionized both our understanding of how genomes function and approaches to the therapy of numerous pathologies. Schistosomes are metazoan parasites and as such utilize most, if not all the epigenetic mechanisms in play in their vertebrate hosts: histone variants, histone tail modifications, non-coding RNA and, perhaps, DNA methylation. Moreover, we are acquiring an increasing understanding of the ways in which these mechanisms come into play during the complex schistosome developmental program. In turn, interest in the actors involved in epigenetic mechanisms, particularly the enzymes that carry out epigenetic modifications of histones or nucleic acid, as therapeutic targets has been stimulated by the finding that their inhibitors exert profound effects, not only on survival, but also on the reproductive function of Schistosoma mansoni. Here, we review our current knowledge, and what we can infer, about the role of epigenetic mechanisms in schistosome development, differentiation and survival. We will consider which epigenetic actors can be targeted for drug discovery and what strategies can be employed to develop potent, selective inhibitors as drugs to cure schistosomiasis.

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Section: Post-translational Modifications Of Histonesmentioning

confidence: 99%

Epigenetic control of gene function in schistosomes: a source of therapeutic targets?

et al. 2014

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“…Also, in vitro assays have identified new compounds that inhibit Sm HDAC8 (class I) [17] and Sm Sirtuins (class III) [19] deacetylases. In addition, in silico analyses [20] have pointed to a large number of S . mansoni histone binding partners potentially involved in the regulation of gene expression, DNA replication, cell death, cellular growth and proliferation [20], thus suggesting that drug-induced histone modifications could affect these cellular processes in the parasite.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni

et al. 2017

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BackgroundSchistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known.Methodology/Principal findingsTSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA, significantly increasing schistosomula mortality.Conclusions/SignificanceGenome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression of dozens of histone reader genes involved in regulation of the epigenetic program in S. mansoni can be used as a starting point to look for possible novel schistosomicidal targets.

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“…Even though mature eggs were used in the present study, it is possible that antigens could have been lost during attainment and handling of the eggs and tissues and during the inoculation of the caudal vein. The vast behavioral diversity of S. mansoni , with its various developmental stages in both vertebrate and intermediate hosts, is a reflection of the large number of genes and their different expression patterns during each stage of the life cycle [45]. One could hypothesize that the S. mansoni SJ strain is different because B. tenagophila is the natural intermediate host.…”

Section: Discussionmentioning

confidence: 99%

A Study of the Granulomatous Responses Induced by Different Strains ofSchistosoma mansoni

Zuim

Allegretti

Linhares

et al. 2012

Interdisciplinary Perspectives on Infectious Diseases

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The increased pathogenesis of the Schistosoma mansoni BH strain compared with the SJ strain has been attributed to the number of granulomas formed in experimental infections, which increase the mortality in definitive hosts. The aim of the present study was to investigate the development of granulomas around the eggs of the S. mansoni BH and SJ strains and to determine whether this host reaction was strain specific. Four experimental groups were analyzed. Two groups contained mice inoculated in the caudal vein with eggs from the S. mansoni BH or SJ strains and the other two contained mice that were infected with cercariae of the BH strain prior to being inoculated with eggs. The number of granulomas per tissue area in the lungs and liver, as well as the size of the granulomas, was analyzed to characterize the response to schistosome infection. The largest granulomatous responses were observed around eggs of the BH strain. Granulomas covered a larger area in the lungs of mice that were previously infected with cercariae and subsequently inoculated with eggs of the BH strain. These results indicated that specific granulomatous responses occurred following an infection with the BH and SJ strains of S. mansoni.

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Schistosoma mansoni histones: From transcription to chromatin regulation; an in silico analysis

Cited by 15 publications

References 55 publications

Epigenetic control of gene function in schistosomes: a source of therapeutic targets?

Epigenetic control of gene function in schistosomes: a source of therapeutic targets?

Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni

A Study of the Granulomatous Responses Induced by Different Strains ofSchistosoma mansoni

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