Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells
Genome-wide analysis of vitamin D receptor (VDR) binding sites in THP-1 human monocyte-like cells highlighted the interleukin 8 gene, also known as chemokine CXC motif ligand 8 (CXCL8). CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of va...
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description | Genome-wide analysis of vitamin D receptor (VDR) binding sites in THP-1 human monocyte-like cells highlighted the interleukin 8 gene, also known as chemokine CXC motif ligand 8 (CXCL8). CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of various cancers. The nine genes of the CXCL cluster and the strong VDR binding site close to the CXCL8 gene are insulated from neighboring genes by CCCTC-binding factor (CTCF) binding sites. Only CXCL8, CXCL6 and CXCL1 are expressed in THP-1 cells, but all three are up-regulated primary 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) target genes. Formaldehyde-assisted isolation of regulatory elements sequencing analysis of the whole CXCL cluster demonstrated 1,25(OH)2D3-dependent chromatin opening exclusively for the VDR binding site. In differentiated THP-1 cells the CXCL8 gene showed a 33-fold higher basal expression, but is together with CXCL6 and CXCL1 still a primary 1,25(OH)2D3 target under the control of the same genomic VDR binding site. In summary, both in undifferentiated and differentiated THP-1 cells the genes CXCL8, CXCL6 and CXCL1 are under the primary control of 1,25(OH)2D3 and its receptor VDR. Our observation provides further evidence for the immune-related functions of vitamin D. |
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CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of various cancers. The nine genes of the CXCL cluster and the strong VDR binding site close to the CXCL8 gene are insulated from neighboring genes by CCCTC-binding factor (CTCF) binding sites. Only CXCL8, CXCL6 and CXCL1 are expressed in THP-1 cells, but all three are up-regulated primary 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) target genes. Formaldehyde-assisted isolation of regulatory elements sequencing analysis of the whole CXCL cluster demonstrated 1,25(OH)2D3-dependent chromatin opening exclusively for the VDR binding site. In differentiated THP-1 cells the CXCL8 gene showed a 33-fold higher basal expression, but is together with CXCL6 and CXCL1 still a primary 1,25(OH)2D3 target under the control of the same genomic VDR binding site. In summary, both in undifferentiated and differentiated THP-1 cells the genes CXCL8, CXCL6 and CXCL1 are under the primary control of 1,25(OH)2D3 and its receptor VDR. Our observation provides further evidence for the immune-related functions of vitamin D.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0078170</identifier><identifier>PMID: 24250750</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Binding Sites ; Calcitriol ; Calcitriol - physiology ; Cancer ; Cell Differentiation ; Cell Line ; Chemokine CXCL1 - genetics ; Chemokine CXCL1 - metabolism ; Chemokine CXCL6 - genetics ; Chemokine CXCL6 - metabolism ; Chemokines ; Chromatin ; Chromatin - genetics ; Chromatin - metabolism ; Clusters ; Cytokines ; Endocrine system ; Enzymes ; Gene expression ; Gene sequencing ; Genes ; Genomes ; Humans ; Interleukin ; Interleukin 8 ; Interleukin-8 - genetics ; Interleukin-8 - metabolism ; Leukemia ; Ligands ; Macrophages ; Macrophages - metabolism ; Monocytes ; Multigene Family ; Prostate ; Proteins ; Receptors, Calcitriol - physiology ; Regulatory sequences ; Signal transduction ; Studies ; Transcription factors ; Transcriptional Activation ; Vitamin D ; Vitamin D receptors ; Vitamin D3</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e78170-e78170</ispartof><rights>2013 Ryynänen, Carlberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Ryynänen, Carlberg 2013 Ryynänen, Carlberg</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4410-ebfdfb4684c5e5dcb8aa5b1d5ceaae7c29c7d3e83f4d9f19d5b4cee5e0a821063</citedby><cites>FETCH-LOGICAL-c4410-ebfdfb4684c5e5dcb8aa5b1d5ceaae7c29c7d3e83f4d9f19d5b4cee5e0a821063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824026/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824026/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24250750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ramagopalan, Sreeram V.</contributor><creatorcontrib>Ryynänen, Jussi</creatorcontrib><creatorcontrib>Carlberg, Carsten</creatorcontrib><title>Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Genome-wide analysis of vitamin D receptor (VDR) binding sites in THP-1 human monocyte-like cells highlighted the interleukin 8 gene, also known as chemokine CXC motif ligand 8 (CXCL8). CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of various cancers. The nine genes of the CXCL cluster and the strong VDR binding site close to the CXCL8 gene are insulated from neighboring genes by CCCTC-binding factor (CTCF) binding sites. Only CXCL8, CXCL6 and CXCL1 are expressed in THP-1 cells, but all three are up-regulated primary 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) target genes. Formaldehyde-assisted isolation of regulatory elements sequencing analysis of the whole CXCL cluster demonstrated 1,25(OH)2D3-dependent chromatin opening exclusively for the VDR binding site. In differentiated THP-1 cells the CXCL8 gene showed a 33-fold higher basal expression, but is together with CXCL6 and CXCL1 still a primary 1,25(OH)2D3 target under the control of the same genomic VDR binding site. In summary, both in undifferentiated and differentiated THP-1 cells the genes CXCL8, CXCL6 and CXCL1 are under the primary control of 1,25(OH)2D3 and its receptor VDR. Our observation provides further evidence for the immune-related functions of vitamin D.</description><subject>Binding Sites</subject><subject>Calcitriol</subject><subject>Calcitriol - physiology</subject><subject>Cancer</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Chemokine CXCL1 - genetics</subject><subject>Chemokine CXCL1 - metabolism</subject><subject>Chemokine CXCL6 - genetics</subject><subject>Chemokine CXCL6 - metabolism</subject><subject>Chemokines</subject><subject>Chromatin</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Clusters</subject><subject>Cytokines</subject><subject>Endocrine system</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genomes</subject><subject>Humans</subject><subject>Interleukin</subject><subject>Interleukin 8</subject><subject>Interleukin-8 - genetics</subject><subject>Interleukin-8 - metabolism</subject><subject>Leukemia</subject><subject>Ligands</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Monocytes</subject><subject>Multigene Family</subject><subject>Prostate</subject><subject>Proteins</subject><subject>Receptors, Calcitriol - physiology</subject><subject>Regulatory sequences</subject><subject>Signal transduction</subject><subject>Studies</subject><subject>Transcription factors</subject><subject>Transcriptional Activation</subject><subject>Vitamin D</subject><subject>Vitamin D receptors</subject><subject>Vitamin D3</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu1DAUjRCIlsIfILDEhgUZ_Mxjg4TKq1IlWMDacuybiaeOPdhJ1fl7HCatWsTKls-55557fYriJcEbwmryfhfm6JXb7IOHDcZ1Q2r8qDglLaNlRTF7fO9-UjxLaYexYE1VPS1OKKcC1wKfFjc_oh1VPCDyjorS2OFgYrg5XNtJjdajTwxFSLlFAhR6NA2ArJ8gOpivMtygLXhA2s0pP2YIDfOoPBqDD_owQYmUN2hUOob9oLZQOnuV6eBcel486ZVL8GI9z4pfXz7_PP9WXn7_enH-8bLUnBNcQtebvuNVw7UAYXTXKCU6YoQGpaDWtNW1YdCwnpu2J60RHdcAArBqKMEVOyteH3X3LiS5Li1JwjmrWkKpyIyLI8MEtZP74z5kUFb-fQhxK1WcrHYgOTSYYVH1uquzJ9YJjIGCrhUHkcGs9WHtNncjGA1-iso9EH2IeDvIbbiWrKEc08Xu21Ught8zpEmONi0LUx7CvPgWbVvTFpNMffMP9f_T8SMr_0FKEfo7MwTLJUi3VXIJklyDlMte3R_krug2OewPOiHIrw</recordid><startdate>20131021</startdate><enddate>20131021</enddate><creator>Ryynänen, Jussi</creator><creator>Carlberg, Carsten</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131021</creationdate><title>Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells</title><author>Ryynänen, Jussi ; Carlberg, Carsten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4410-ebfdfb4684c5e5dcb8aa5b1d5ceaae7c29c7d3e83f4d9f19d5b4cee5e0a821063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Binding Sites</topic><topic>Calcitriol</topic><topic>Calcitriol - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ryynänen, Jussi</au><au>Carlberg, Carsten</au><au>Ramagopalan, Sreeram V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-10-21</date><risdate>2013</risdate><volume>8</volume><issue>10</issue><spage>e78170</spage><epage>e78170</epage><pages>e78170-e78170</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Genome-wide analysis of vitamin D receptor (VDR) binding sites in THP-1 human monocyte-like cells highlighted the interleukin 8 gene, also known as chemokine CXC motif ligand 8 (CXCL8). CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of various cancers. The nine genes of the CXCL cluster and the strong VDR binding site close to the CXCL8 gene are insulated from neighboring genes by CCCTC-binding factor (CTCF) binding sites. Only CXCL8, CXCL6 and CXCL1 are expressed in THP-1 cells, but all three are up-regulated primary 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) target genes. Formaldehyde-assisted isolation of regulatory elements sequencing analysis of the whole CXCL cluster demonstrated 1,25(OH)2D3-dependent chromatin opening exclusively for the VDR binding site. In differentiated THP-1 cells the CXCL8 gene showed a 33-fold higher basal expression, but is together with CXCL6 and CXCL1 still a primary 1,25(OH)2D3 target under the control of the same genomic VDR binding site. In summary, both in undifferentiated and differentiated THP-1 cells the genes CXCL8, CXCL6 and CXCL1 are under the primary control of 1,25(OH)2D3 and its receptor VDR. Our observation provides further evidence for the immune-related functions of vitamin D.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24250750</pmid><doi>10.1371/journal.pone.0078170</doi><oa>free_for_read</oa></addata></record> |
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subjects | Binding Sites Calcitriol Calcitriol - physiology Cancer Cell Differentiation Cell Line Chemokine CXCL1 - genetics Chemokine CXCL1 - metabolism Chemokine CXCL6 - genetics Chemokine CXCL6 - metabolism Chemokines Chromatin Chromatin - genetics Chromatin - metabolism Clusters Cytokines Endocrine system Enzymes Gene expression Gene sequencing Genes Genomes Humans Interleukin Interleukin 8 Interleukin-8 - genetics Interleukin-8 - metabolism Leukemia Ligands Macrophages Macrophages - metabolism Monocytes Multigene Family Prostate Proteins Receptors, Calcitriol - physiology Regulatory sequences Signal transduction Studies Transcription factors Transcriptional Activation Vitamin D Vitamin D receptors Vitamin D3 |
title | Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells |
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