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dc.contributor.authorSantoni, Federico A.
dc.contributor.authorGuerra, Jessica
dc.contributor.authorLuban, Jeremy
dc.date2022-08-11T08:09:41.000
dc.date.accessioned2022-08-23T16:39:58Z
dc.date.available2022-08-23T16:39:58Z
dc.date.issued2012-12-20
dc.date.submitted2013-03-04
dc.identifier.citationRetrovirology. 2012 Dec 20;9:111. doi: 10.1186/1742-4690-9-111. <a href="http://dx.doi.org/10.1186/1742-4690-9-111">Link to article on publisher's site</a>
dc.identifier.issn1742-4690 (Linking)
dc.identifier.doi10.1186/1742-4690-9-111
dc.identifier.pmid23253934
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39588
dc.description.abstractBACKGROUND: Certain post-translational modifications to histones, including H3K4me3, as well as binding sites for the transcription factor STAT1, predict the site of integration of exogenous gamma-retroviruses with great accuracy and cell-type specificity. Statistical methods that were used to identify chromatin features that predict exogenous gamma-retrovirus integration site selection were exploited here to determine whether cell type-specific chromatin markers are enriched in the vicinity of endogenous retroviruses (ERVs). RESULTS: Among retro-elements in the human genome, the gamma-retrovirus HERV-H was highly associated with H3K4me3, though this association was only observed in embryonic stem (ES) cells (p < 10-300) and, to a lesser extent, in induced pluripotent stem (iPS) cells. No significant association was observed in nearly 40 differentiated cell types, nor was any association observed with other retro-elements. Similar strong association was observed between HERV-H and the binding sites within ES cells for the pluripotency transcription factors NANOG, OCT4, and SOX2. NANOG binding sites were located within the HERV-H 5'LTR itself. OCT4 and SOX2 binding sites were within 1 kB and 2 kB of the 5'LTR, respectively. In keeping with these observations, HERV-H RNA constituted 2% of all poly A RNA in ES cells. As ES cells progressed down a differentiation pathway, the levels of HERV-H RNA decreased progressively. RNA-Seq datasets showed HERV-H transcripts to be over 5 kB in length and to have the structure 5'LTR-gag-pro-3'LTR, with no evidence of splicing and no intact open reading frames. CONCLUSION: The developmental regulation of HERV-H expression, the association of HERV-H with binding sites for pluripotency transcription factors, and the extremely high levels of HERV-H RNA in human ES cells suggest that HERV-H contributes to pluripotency in human cells. Proximity of HERV-H to binding sites for pluripotency transcription factors within ES cells might be due to retention of the same chromatin features that determined the site of integration of the ancestral, exogenous, gamma-retrovirus that gave rise to HERV-H in the distant past. Retention of these markers, or, alternatively, recruitment of them to the site of the established provirus, may have acted post-integration to fix the provirus within the germ-line of the host species. Either way, HERV-H RNA provides a specific marker for pluripotency in human cells.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23253934&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>© 2012 Santoni et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
dc.subjectRetroviridae Proteins
dc.subjectHistones
dc.subjectPluripotent Stem Cells
dc.subjectEmbryonic Stem Cells
dc.subjectCell and Developmental Biology
dc.subjectVirology
dc.titleHERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency
dc.typeJournal Article
dc.source.journaltitleRetrovirology
dc.source.volume9
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3382&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2382
dc.identifier.contextkey3830682
refterms.dateFOA2022-08-23T16:39:59Z
html.description.abstract<p>BACKGROUND: Certain post-translational modifications to histones, including H3K4me3, as well as binding sites for the transcription factor STAT1, predict the site of integration of exogenous gamma-retroviruses with great accuracy and cell-type specificity. Statistical methods that were used to identify chromatin features that predict exogenous gamma-retrovirus integration site selection were exploited here to determine whether cell type-specific chromatin markers are enriched in the vicinity of endogenous retroviruses (ERVs).</p> <p>RESULTS: Among retro-elements in the human genome, the gamma-retrovirus HERV-H was highly associated with H3K4me3, though this association was only observed in embryonic stem (ES) cells (p < 10-300) and, to a lesser extent, in induced pluripotent stem (iPS) cells. No significant association was observed in nearly 40 differentiated cell types, nor was any association observed with other retro-elements. Similar strong association was observed between HERV-H and the binding sites within ES cells for the pluripotency transcription factors NANOG, OCT4, and SOX2. NANOG binding sites were located within the HERV-H 5'LTR itself. OCT4 and SOX2 binding sites were within 1 kB and 2 kB of the 5'LTR, respectively. In keeping with these observations, HERV-H RNA constituted 2% of all poly A RNA in ES cells. As ES cells progressed down a differentiation pathway, the levels of HERV-H RNA decreased progressively. RNA-Seq datasets showed HERV-H transcripts to be over 5 kB in length and to have the structure 5'LTR-gag-pro-3'LTR, with no evidence of splicing and no intact open reading frames.</p> <p>CONCLUSION: The developmental regulation of HERV-H expression, the association of HERV-H with binding sites for pluripotency transcription factors, and the extremely high levels of HERV-H RNA in human ES cells suggest that HERV-H contributes to pluripotency in human cells. Proximity of HERV-H to binding sites for pluripotency transcription factors within ES cells might be due to retention of the same chromatin features that determined the site of integration of the ancestral, exogenous, gamma-retrovirus that gave rise to HERV-H in the distant past. Retention of these markers, or, alternatively, recruitment of them to the site of the established provirus, may have acted post-integration to fix the provirus within the germ-line of the host species. Either way, HERV-H RNA provides a specific marker for pluripotency in human cells.</p>
dc.identifier.submissionpathoapubs/2382
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages111


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