Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes
J. Neurochem. (2010) 115, 1409-1420. ABSTRACT: Myelination of peripheral nerves by Schwann cells depends upon a gene regulatory network controlled by early growth response Egr2/Krox20, which is specifically required for Schwann cells to initiate and maintain myelination. To elucidate the mechanism b...
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| description | J. Neurochem. (2010) 115, 1409-1420. ABSTRACT: Myelination of peripheral nerves by Schwann cells depends upon a gene regulatory network controlled by early growth response Egr2/Krox20, which is specifically required for Schwann cells to initiate and maintain myelination. To elucidate the mechanism by which Egr2 regulates gene expression during myelination, we have performed chromatin immunoprecipitation analysis on myelinating rat sciatic nerve in vivo. The resulting samples were applied to a tiled microarray consisting of a broad spectrum of genes that are activated or repressed in Egr2-deficient mice. The results show extensive binding within myelin-associated genes, as well as some genes that become repressed in myelinating Schwann cells. Many of the Egr2 peaks coincide with regions of open chromatin, which is a marker of enhancer regions. In addition, further analysis showed that there is substantial colocalization of Egr2 binding with Sox10, a transcription factor required for Schwann cell specification and other stages of Schwann cell development. Finally, we have found that Egr2 binds to promoters of several lipid biosynthetic genes, which is consistent with their dramatic up-regulation during the formation of lipid-rich myelin. Overall, this analysis provides a locus-wide profile of Egr2 binding patterns in major myelin-associated genes using myelinating peripheral nerve. |
| doi_str_mv | 10.1111/j.1471-4159.2010.07045.x |
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Neurochem. (2010) 115, 1409-1420. ABSTRACT: Myelination of peripheral nerves by Schwann cells depends upon a gene regulatory network controlled by early growth response Egr2/Krox20, which is specifically required for Schwann cells to initiate and maintain myelination. To elucidate the mechanism by which Egr2 regulates gene expression during myelination, we have performed chromatin immunoprecipitation analysis on myelinating rat sciatic nerve in vivo. The resulting samples were applied to a tiled microarray consisting of a broad spectrum of genes that are activated or repressed in Egr2-deficient mice. The results show extensive binding within myelin-associated genes, as well as some genes that become repressed in myelinating Schwann cells. Many of the Egr2 peaks coincide with regions of open chromatin, which is a marker of enhancer regions. In addition, further analysis showed that there is substantial colocalization of Egr2 binding with Sox10, a transcription factor required for Schwann cell specification and other stages of Schwann cell development. Finally, we have found that Egr2 binds to promoters of several lipid biosynthetic genes, which is consistent with their dramatic up-regulation during the formation of lipid-rich myelin. Overall, this analysis provides a locus-wide profile of Egr2 binding patterns in major myelin-associated genes using myelinating peripheral nerve.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/j.1471-4159.2010.07045.x</identifier><identifier>PMID: 21044070</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Animals, Newborn ; Binding sites ; Biological and medical sciences ; Cell Line, Tumor ; Cellular biology ; ChIP ; Chromatin ; DNA microarrays ; Early Growth Response Protein 2 - genetics ; Early Growth Response Protein 2 - metabolism ; EGR-2 protein ; Enhancers ; Ether-A-Go-Go Potassium Channels - genetics ; Ether-A-Go-Go Potassium Channels - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Regulation - physiology ; Gene Targeting - methods ; Genes. Genome ; Genetic Loci - genetics ; Immunoprecipitation ; Krox-20 protein ; Krox20 ; Lipids ; Melanoma, Experimental - genetics ; Mice ; Molecular and cellular biology ; Molecular genetics ; Myelin Sheath - genetics ; Myelin Sheath - metabolism ; Myelination ; Neurochemistry ; Neurons ; Peripheral nerves ; Promoters ; Rats ; Rats, Sprague-Dawley ; Schwann ; Schwann cells ; Sciatic nerve ; Sciatic Nerve - physiology ; Sox10 protein ; Transcription factors ; Transcription. Transcription factor. Splicing. Rna processing</subject><ispartof>Journal of neurochemistry, 2010-12, Vol.115 (6), p.1409-1420</ispartof><rights>2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry</rights><rights>2015 INIST-CNRS</rights><rights>2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6525-c3f86c61ab0817753424b6f77133e1fcacd41189b008657e811c34489bb3fd483</citedby><cites>FETCH-LOGICAL-c6525-c3f86c61ab0817753424b6f77133e1fcacd41189b008657e811c34489bb3fd483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1471-4159.2010.07045.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1471-4159.2010.07045.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1413,1429,27906,27907,45556,45557,46391,46815</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23630865$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21044070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jang, Sung-Wook</creatorcontrib><creatorcontrib>Srinivasan, Rajini</creatorcontrib><creatorcontrib>Jones, Erin A</creatorcontrib><creatorcontrib>Sun, Guannan</creatorcontrib><creatorcontrib>Keles, Sunduz</creatorcontrib><creatorcontrib>Krueger, Courtney</creatorcontrib><creatorcontrib>Chang, Li-Wei</creatorcontrib><creatorcontrib>Nagarajan, Rakesh</creatorcontrib><creatorcontrib>Svaren, John</creatorcontrib><title>Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>J. Neurochem. (2010) 115, 1409-1420. ABSTRACT: Myelination of peripheral nerves by Schwann cells depends upon a gene regulatory network controlled by early growth response Egr2/Krox20, which is specifically required for Schwann cells to initiate and maintain myelination. To elucidate the mechanism by which Egr2 regulates gene expression during myelination, we have performed chromatin immunoprecipitation analysis on myelinating rat sciatic nerve in vivo. The resulting samples were applied to a tiled microarray consisting of a broad spectrum of genes that are activated or repressed in Egr2-deficient mice. The results show extensive binding within myelin-associated genes, as well as some genes that become repressed in myelinating Schwann cells. Many of the Egr2 peaks coincide with regions of open chromatin, which is a marker of enhancer regions. In addition, further analysis showed that there is substantial colocalization of Egr2 binding with Sox10, a transcription factor required for Schwann cell specification and other stages of Schwann cell development. Finally, we have found that Egr2 binds to promoters of several lipid biosynthetic genes, which is consistent with their dramatic up-regulation during the formation of lipid-rich myelin. Overall, this analysis provides a locus-wide profile of Egr2 binding patterns in major myelin-associated genes using myelinating peripheral nerve.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Binding sites</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cellular biology</subject><subject>ChIP</subject><subject>Chromatin</subject><subject>DNA microarrays</subject><subject>Early Growth Response Protein 2 - genetics</subject><subject>Early Growth Response Protein 2 - metabolism</subject><subject>EGR-2 protein</subject><subject>Enhancers</subject><subject>Ether-A-Go-Go Potassium Channels - genetics</subject><subject>Ether-A-Go-Go Potassium Channels - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - physiology</subject><subject>Gene Targeting - methods</subject><subject>Genes. Genome</subject><subject>Genetic Loci - genetics</subject><subject>Immunoprecipitation</subject><subject>Krox-20 protein</subject><subject>Krox20</subject><subject>Lipids</subject><subject>Melanoma, Experimental - genetics</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Myelin Sheath - genetics</subject><subject>Myelin Sheath - metabolism</subject><subject>Myelination</subject><subject>Neurochemistry</subject><subject>Neurons</subject><subject>Peripheral nerves</subject><subject>Promoters</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Schwann</subject><subject>Schwann cells</subject><subject>Sciatic nerve</subject><subject>Sciatic Nerve - physiology</subject><subject>Sox10 protein</subject><subject>Transcription factors</subject><subject>Transcription. Transcription factor. Splicing. Rna processing</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU2P0zAQhi0EYsvCX4AICXFK12M7jnsACVXL11ZwgD1bjmsHV2m82Anb_nsmtJSPC1iybI2fdzwzLyEF0DngutjMQdRQCqgWc0YxSmsqqvnuDpmdHu6SGaWMlZwKdkYe5LyhFKSQcJ-cMaBCoGZGrlbRjrm8DWtX4O6H4IM1Q4h9EX1x2SZ2cZXijtEiuXbszBDTvhhMat2Qi9AX273r8Ghd7_JDcs-bLrtHx_OcXL--_Lx8W64-vnm3fLUqraxYVVrulbQSTEMV1HXFBRON9HUNnDvw1ti1AFCLhlIlq9opAMuFwEDD_Voofk5eHvLejM3WrS1WnUynb1LYmrTX0QT950sfvug2ftOcSUqrChM8PyZI8evo8qC3IVvXdaZ3ccxaVbKulWDy3yQoQTmIBZJP_yI3cUw9zgGhimE_C4qQOkA2xZyT86eigerJWb3Rk4F6MlBPzuofzuodSh__3vRJ-NNKBJ4dAZOt6XwyvQ35F8cln-aJ3IsDdxs6t__vAvT7D8vphvonB703UZs24R_Xn5DkFBag0Ez-HdJfxkQ</recordid><startdate>201012</startdate><enddate>201012</enddate><creator>Jang, Sung-Wook</creator><creator>Srinivasan, Rajini</creator><creator>Jones, Erin A</creator><creator>Sun, Guannan</creator><creator>Keles, Sunduz</creator><creator>Krueger, Courtney</creator><creator>Chang, Li-Wei</creator><creator>Nagarajan, Rakesh</creator><creator>Svaren, John</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</general><scope>FBQ</scope><scope>IQODW</scope><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>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>201012</creationdate><title>Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes</title><author>Jang, Sung-Wook ; Srinivasan, Rajini ; Jones, Erin A ; Sun, Guannan ; Keles, Sunduz ; Krueger, Courtney ; Chang, Li-Wei ; Nagarajan, Rakesh ; Svaren, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6525-c3f86c61ab0817753424b6f77133e1fcacd41189b008657e811c34489bb3fd483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Binding sites</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cellular biology</topic><topic>ChIP</topic><topic>Chromatin</topic><topic>DNA microarrays</topic><topic>Early Growth Response Protein 2 - genetics</topic><topic>Early Growth Response Protein 2 - metabolism</topic><topic>EGR-2 protein</topic><topic>Enhancers</topic><topic>Ether-A-Go-Go Potassium Channels - genetics</topic><topic>Ether-A-Go-Go Potassium Channels - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - physiology</topic><topic>Gene Targeting - methods</topic><topic>Genes. Genome</topic><topic>Genetic Loci - genetics</topic><topic>Immunoprecipitation</topic><topic>Krox-20 protein</topic><topic>Krox20</topic><topic>Lipids</topic><topic>Melanoma, Experimental - genetics</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Myelin Sheath - genetics</topic><topic>Myelin Sheath - metabolism</topic><topic>Myelination</topic><topic>Neurochemistry</topic><topic>Neurons</topic><topic>Peripheral nerves</topic><topic>Promoters</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Schwann</topic><topic>Schwann cells</topic><topic>Sciatic nerve</topic><topic>Sciatic Nerve - physiology</topic><topic>Sox10 protein</topic><topic>Transcription factors</topic><topic>Transcription. Transcription factor. Splicing. 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Neurochem. (2010) 115, 1409-1420. ABSTRACT: Myelination of peripheral nerves by Schwann cells depends upon a gene regulatory network controlled by early growth response Egr2/Krox20, which is specifically required for Schwann cells to initiate and maintain myelination. To elucidate the mechanism by which Egr2 regulates gene expression during myelination, we have performed chromatin immunoprecipitation analysis on myelinating rat sciatic nerve in vivo. The resulting samples were applied to a tiled microarray consisting of a broad spectrum of genes that are activated or repressed in Egr2-deficient mice. The results show extensive binding within myelin-associated genes, as well as some genes that become repressed in myelinating Schwann cells. Many of the Egr2 peaks coincide with regions of open chromatin, which is a marker of enhancer regions. In addition, further analysis showed that there is substantial colocalization of Egr2 binding with Sox10, a transcription factor required for Schwann cell specification and other stages of Schwann cell development. Finally, we have found that Egr2 binds to promoters of several lipid biosynthetic genes, which is consistent with their dramatic up-regulation during the formation of lipid-rich myelin. Overall, this analysis provides a locus-wide profile of Egr2 binding patterns in major myelin-associated genes using myelinating peripheral nerve.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21044070</pmid><doi>10.1111/j.1471-4159.2010.07045.x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Newborn Binding sites Biological and medical sciences Cell Line, Tumor Cellular biology ChIP Chromatin DNA microarrays Early Growth Response Protein 2 - genetics Early Growth Response Protein 2 - metabolism EGR-2 protein Enhancers Ether-A-Go-Go Potassium Channels - genetics Ether-A-Go-Go Potassium Channels - metabolism Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Regulation - physiology Gene Targeting - methods Genes. Genome Genetic Loci - genetics Immunoprecipitation Krox-20 protein Krox20 Lipids Melanoma, Experimental - genetics Mice Molecular and cellular biology Molecular genetics Myelin Sheath - genetics Myelin Sheath - metabolism Myelination Neurochemistry Neurons Peripheral nerves Promoters Rats Rats, Sprague-Dawley Schwann Schwann cells Sciatic nerve Sciatic Nerve - physiology Sox10 protein Transcription factors Transcription. Transcription factor. Splicing. Rna processing |
| title | Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes |
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