Journal article
Dimethylated H3K27 Is a Repressive Epigenetic Histone Mark in the Protist Entamoeba histolytica and Is Significantly Enriched in Genes Silenced via the RNAi Pathway
The Journal of biological chemistry, Vol.290(34), pp.21114-21130
08/21/2015
DOI: 10.1074/jbc.M115.647263
PMID: 26149683
Abstract
RNA interference (RNAi) is a fundamental biological process that plays a crucial role in regulation of gene expression in many organisms. Transcriptional gene silencing (TGS) is one of the important nuclear roles of RNAi. Our previous data show that Entamoeba histolytica has a robust RNAi pathway that links to TGS via Argonaute 2-2 (Ago2-2) associated 27-nucleotide small RNAs with 5′-polyphosphate termini. Here, we report the first repressive histone mark to be identified in E. histolytica, dimethylation of H3K27 (H3K27Me2), and demonstrate that it is enriched at genes that are silenced by RNAi-mediated TGS. An RNAi-silencing trigger can induce H3K27Me2 deposits at both episomal and chromosomal loci, mediating gene silencing. Our data support two phases of RNAi-mediated TGS: an active silencing phase where the RNAi trigger is present and both H3K27Me2 and Ago2-2 concurrently enrich at chromosomal loci; and an established silencing phase in which the RNAi trigger is removed, but gene silencing with H3K27Me2 enrichment persist independently of Ago2-2 deposition. Importantly, some genes display resistance to chromosomal silencing despite induction of functional small RNAs. In those situations, the RNAi-triggering plasmid that is maintained episomally gets partially silenced and has H3K27Me2 enrichment, but the chromosomal copy displays no repressive histone enrichment. Our data are consistent with a model in which H3K27Me2 is a repressive histone modification, which is strongly associated with transcriptional repression. This is the first example of an epigenetic histone modification that functions to mediate RNAi-mediated TGS in the deep-branching eukaryote E. histolytica.
Background:Entamoeba histolytica has an RNAi-mediated TGS pathway but the epigenetic marks are not known.
Results: H3K27Me2 is an inducible repressive histone modification enriched in loci silenced by small RNAs.
Conclusion: Transcriptional gene silencing and chromatin modification are coupled to maintain prolonged gene silencing.
Significance: This work identifies the first repressive histone mark in Entamoeba and links it to RNAi.
Details
- Title: Subtitle
- Dimethylated H3K27 Is a Repressive Epigenetic Histone Mark in the Protist Entamoeba histolytica and Is Significantly Enriched in Genes Silenced via the RNAi Pathway
- Creators
- Bardees M. Foda - Stanford MedicineUpinder Singh - Stanford University
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.290(34), pp.21114-21130
- DOI
- 10.1074/jbc.M115.647263
- PMID
- 26149683
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Number of pages
- 17
- Grant note
- R01AI053724; R21 AI102277 / National Institutes of Health
- Language
- English
- Date published
- 08/21/2015
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985244556002771
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