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Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis
Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepre...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2017
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577184/ https://www.ncbi.nlm.nih.gov/pubmed/28855511 http://dx.doi.org/10.1038/s41467-017-00517-4 |
| _version_ | 1783260304075915264 |
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| author | Liu, Yongmei Reynolds, Lindsay M. Ding, Jingzhong Hou, Li Lohman, Kurt Young, Tracey Cui, Wei Huang, Zhiqing Grenier, Carole Wan, Ma Stunnenberg, Hendrik G. Siscovick, David Hou, Lifang Psaty, Bruce M. Rich, Stephen S. Rotter, Jerome I. Kaufman, Joel D. Burke, Gregory L. Murphy, Susan Jacobs, David R. Post, Wendy Hoeschele, Ina Bell, Douglas A. Herrington, David Parks, John S. Tracy, Russell P. McCall, Charles E. Stein, James H. |
| author_facet | Liu, Yongmei Reynolds, Lindsay M. Ding, Jingzhong Hou, Li Lohman, Kurt Young, Tracey Cui, Wei Huang, Zhiqing Grenier, Carole Wan, Ma Stunnenberg, Hendrik G. Siscovick, David Hou, Lifang Psaty, Bruce M. Rich, Stephen S. Rotter, Jerome I. Kaufman, Joel D. Burke, Gregory L. Murphy, Susan Jacobs, David R. Post, Wendy Hoeschele, Ina Bell, Douglas A. Herrington, David Parks, John S. Tracy, Russell P. McCall, Charles E. Stein, James H. |
| author_sort | Liu, Yongmei |
| collection | PubMed |
| description | Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype. |
| format | Online Article Text |
| id | pubmed-5577184 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-55771842017-09-01 Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis Liu, Yongmei Reynolds, Lindsay M. Ding, Jingzhong Hou, Li Lohman, Kurt Young, Tracey Cui, Wei Huang, Zhiqing Grenier, Carole Wan, Ma Stunnenberg, Hendrik G. Siscovick, David Hou, Lifang Psaty, Bruce M. Rich, Stephen S. Rotter, Jerome I. Kaufman, Joel D. Burke, Gregory L. Murphy, Susan Jacobs, David R. Post, Wendy Hoeschele, Ina Bell, Douglas A. Herrington, David Parks, John S. Tracy, Russell P. McCall, Charles E. Stein, James H. Nat Commun Article Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype. Nature Publishing Group UK 2017-08-30 /pmc/articles/PMC5577184/ /pubmed/28855511 http://dx.doi.org/10.1038/s41467-017-00517-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Liu, Yongmei Reynolds, Lindsay M. Ding, Jingzhong Hou, Li Lohman, Kurt Young, Tracey Cui, Wei Huang, Zhiqing Grenier, Carole Wan, Ma Stunnenberg, Hendrik G. Siscovick, David Hou, Lifang Psaty, Bruce M. Rich, Stephen S. Rotter, Jerome I. Kaufman, Joel D. Burke, Gregory L. Murphy, Susan Jacobs, David R. Post, Wendy Hoeschele, Ina Bell, Douglas A. Herrington, David Parks, John S. Tracy, Russell P. McCall, Charles E. Stein, James H. Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis |
| title | Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis |
| title_full | Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis |
| title_fullStr | Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis |
| title_full_unstemmed | Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis |
| title_short | Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis |
| title_sort | blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577184/ https://www.ncbi.nlm.nih.gov/pubmed/28855511 http://dx.doi.org/10.1038/s41467-017-00517-4 |
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