dc.creator | Nataf, Serge | es |
dc.creator | Uriagereka, Juan | es |
dc.creator | Benítez Burraco, Antonio | es |
dc.date.accessioned | 2019-09-19T07:17:47Z | |
dc.date.available | 2019-09-19T07:17:47Z | |
dc.date.issued | 2019-04-12 | |
dc.identifier.citation | Nataf, S., Uriagereka, J. y Benítez Burraco, A. (2019). The promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MEr41 primate-specific endogenous retrovirus: An evolutionary connection between immunity and cognition. Frontiers in Genetics, 10, 321-1-321-13. | |
dc.identifier.issn | 1664-8021 | es |
dc.identifier.uri | https://hdl.handle.net/11441/89197 | |
dc.description | The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fgene.2019.00321/full#supplementary-material | es |
dc.description.abstract | Social behavior and neuronal connectivity in rodents have been shown to be shaped by the prototypical T lymphocyte-derived pro-inflammatory cytokine Interferon-gamma (IFNγ). It has also been demonstrated that STAT1 (Signal Transducer And Activator Of Transcription 1), a transcription factor (TF) crucially involved in the IFNγ pathway, binds consensus sequences that, in humans, are located with a high frequency in the LTRs (Long Terminal Repeats) of the MER41 family of primate-specific HERVs (Human Endogenous Retroviruses). However, the putative role of an IFNγ/STAT1/MER41 pathway in human cognition and/or behavior is still poorly documented. Here, we present evidence that the promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MER41 HERVs. This observation is specific to MER41 among more than 130 HERVs examined. Moreover, we have not found such a significant enrichment in the promoter regions of genes that associate with autism spectrum disorder (ASD) or schizophrenia. Interestingly, ID-associated genes exhibit promoter-localized MER41 LTRs that harbor TF binding sites (TFBSs) for not only STAT1 but also other immune TFs such as, in particular, NFKB1 (Nuclear Factor Kappa B Subunit 1) and STAT3 (Signal Transducer And Activator Of Transcription 3). Moreover, IL-6 (Interleukin 6) rather than IFNγ, is identified as the main candidate cytokine regulating such an immune/MER41/cognition pathway. Of note, differences between humans and chimpanzees are observed regarding the insertion sites of MER41 LTRs in the promoter regions of ID-associated genes. Finally, a survey of the human proteome has allowed us to map a protein-protein network which links the identified immune/MER41/cognition pathway to FOXP2 (Forkhead Box P2), a key TF involved in the emergence of human speech. Our work suggests that together with the evolution of immune genes, the stepped self-domestication of MER41 in the genomes of primates could have contributed to cognitive evolution. We further propose that non-inherited forms of ID might result from the untimely or quantitatively inappropriate expression of immune signals, notably IL-6, that putatively regulate cognition-associated genes via promoter-localized MER41 LTRs. | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Frontiers Research Foundation | es |
dc.relation.ispartof | Frontiers in Genetics, 10, 321-1-321-13. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Intellectual disability | es |
dc.subject | Cognition | es |
dc.subject | Innate immunity | es |
dc.subject | Evolution | es |
dc.subject | HERV | es |
dc.title | The promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MEr41 primate-specific endogenous retrovirus: An evolutionary connection between immunity and cognition | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Lengua Española, Lingüística y Teoría de la Literatura | es |
dc.relation.publisherversion | https://doi.org/10.3389/fgene.2019.00321 | es |
dc.identifier.doi | 10.3389/fgene.2019.00321 | es |
idus.format.extent | 13 p. | es |
dc.journaltitle | Frontiers in Genetics | es |
dc.publication.volumen | 10 | es |
dc.publication.initialPage | 321-1 | es |
dc.publication.endPage | 321-13 | es |