{"id":657,"date":"2017-03-14T11:51:31","date_gmt":"2017-03-14T02:51:31","guid":{"rendered":"http:\/\/www2.med.osaka-u.ac.jp\/wwwmed\/eng\/activities\/results\/2009year\/ura-kiyoe-kaneda-yasufumi"},"modified":"2017-04-28T15:33:01","modified_gmt":"2017-04-28T06:33:01","slug":"article06","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2009year\/article06","title":{"rendered":"URA Kiyoe, KANEDA Yasufumi \u226aGene Therapy Science\u226b <span>\u201cA histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome\u201d<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2009year\/article06\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><!-- \n\n<h1>\u6d66 \u8056\u6075\u3001\u91d1\u7530 \u5b89\u53f2 \u226a\u907a\u4f1d\u5b50\u6cbb\u7642\u5b66\u226b<\/h1>\n\n --><\/p>\n<p class=\"figure\"><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2009\/kaneda20090602_1.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2009\/kaneda20090602_1.jpeg\" alt=\"\" height=\"133\" width=\"200\" \/><br \/><span class=\"click\">Click to enlarge<\/span><\/a><\/p>\n<p>  <a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2009\/kaneda20090602_2.jpeg\" target=\"_blank\" class=\"zoom\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/\/activities\/results\/2009\/kaneda20090602_2.jpeg\" alt=\"\" height=\"133\" width=\"200\" \/><br \/><span class=\"click\">Click to enlarge<\/span><\/a><\/p>\n<p>2009-6-1<br \/>\n  <span class=\"lineFrame\">Publish<\/span> Nature,460:287-91,2009<\/p>\n<p><!-- \n\n<h3>\u30d2\u30b9\u30c8\u30f3H3K36\u30c8\u30ea\u30e1\u30c1\u30eb\u5316\u9175\u7d20WHSC1\u306e\u7570\u5e38\u306fNkx2-5\u306a\u3069\u306e\u8ee2\u5199\u56e0\u5b50\u6a5f\u80fd\u969c\u5bb3\u306b\u3088\u3063\u3066\uff14p\u75c7\u5019\u7fa4\u3092\u5f15\u304d\u8d77\u3053\u3059<\/h3>\n\n\n\n\n<p>\u30d2\u30b9\u30c8\u30f3\u4fee\u98fe\u306f\u3001\u69d8\u3005\u306a\u9175\u7d20\u306b\u3088\u3063\u3066\u62c5\u308f\u308c\u3001\u7279\u7570\u7684\u306a\u30bf\u30f3\u30d1\u30af\u8cea\u306b\u3088\u3063\u3066\u8a8d\u8b58\u3055\u308c\u3066\u8ee2\u5199\u5236\u5fa1\u30b7\u30b0\u30ca\u30eb\u3068\u3057\u3066\u6a5f  \u80fd\u3059\u308b\u3002\u4e2d\u3067\u3082\u30d2\u30b9\u30c8\u30f3H\uff13\u306e\uff13\uff16\u756a\u76ee\u30ea\u30b7\u30f3\u6b8b\u57fa\u306e\u30c8\u30ea\u30e1\u30c1\u30eb\u5316(H3K36me3)\u306f\u3001\u7a2e\u3092\u8d8a\u3048\u3066\u8ee2\u5199\u6d3b\u6027\u306e\u9ad8\u3044\u30b2\u30ce\u30e0\u9818\u57df\u306b\u5b58\u5728\u3057\u3001\u4eca\u65e5\u3001\u9032\u884c\u4e2d\u306e\u8ee2\u5199\u30de\u30fc\u30af\u3068\u3057\u3066\u6349\u3048\u3089\u308c\u3066\u3044\u308b\u3002\u3057\u304b\u3057\u9ad8\u7b49\u771f\u6838\u751f\u7269\u306b\u304a\u3051\u308bH3K36me3\u306e\u5236\u5fa1\u304a\u3088\u3073\u305d\u306e\u6a5f\u80fd\u306f\u672a\u3060\u306b\u826f\u304f\u5206\u304b\u3063\u3066\u3044\u306a\u3044\u3002\u4eca\u56de\u3001\u79c1\u305f\u3061\u306f\u5fc3\u75be\u60a3\u3001\u7cbe\u795e\u9045\u6ede\u3001\u767a\u80b2\u4e0d\u826f\u306a\u3069\u3092\u7279\u5fb4\u3068\u3059\u308b4p\u75c7\u5019\u7fa4\u306e\uff14\u756a\u67d3\u8272\u4f53\u6b20\u640d\u9818\u57df\u306b\u3042\u308bWolf-Hirschhorn syndrome candidate 1 \u907a\u4f1d\u5b50\uff08WHSC1\uff09\u304cH3K36me3\u9175\u7d20\u3067\u3042\u308a\u3001\u30de\u30a6\u30b9ES\u7d30\u80de\u3067\u306f\u8ee2\u5199\u5236\u5fa1\u56e0\u5b50Nanog\u3001Sall1\u3001Sall4\u3068\u30de\u30a6\u30b9\u80ce\u5150\u5fc3\u81d3\u3067\u306f\u5fc3\u81d3\u5f62\u6210\u8ee2  \u5199\u56e0\u5b50Nkx2.5\u3068\u8907\u5408\u4f53\u3092\u5f62\u6210\u3057\u3066\u3001\u305d\u308c\u305e\u308c\u306e\u30bf\u30fc\u30b2\u30c3\u30c8\u907a\u4f1d\u5b50\u306e\u8ee2\u5199\u767a\u73fe\u3092\u8abf\u7bc0\u3059\u308b\u3053\u3068\u3092\u898b\u51fa\u3057\u305f\u3002Whsc1\u6b20\u640d\u30de\u30a6\u30b9\u306f\uff14p\u75c7\u5019\u7fa4\u3067\u898b\u3089\u308c\u308b\u3088\u3046\u306b\u5fc3\u81d3\u306e\u5fc3\u623f\u30fb\u5fc3\u5ba4\u4e2d\u9694\u6b20\u640d\u306a\u3069\u6b63\u4e2d\u7dda\u306b\u6cbf\u3063\u305f\u69d8\u3005\u306a\u5f62\u614b\u7570\u5e38\u3092\u793a\u3057\u767a\u80b2\u4e0d\u826f\u3067\u51fa\u751f\u76f4\u5f8c\u306b\u6b7b\u4ea1\u3059\u308b\u3002\u5b9f\u969b\u306b\u907a\u4f1d\u5b66\u7684\u76f8\u4e92\u4f5c\u7528\u304c<em>Nkx2.5<\/em>\u3068<em>Whsc1<\/em>\u306e\u4e21\u907a\u4f1d\u5b50\u9593\u306b\u8a8d\u3081\u3089\u308c\u305f\u3002\u4ee5\u4e0a\u306e\u7d50\u679c\u304b\u3089H3K36me3\u9175\u7d20Whsc1\u304c\u3001Nkx2-5\u3092\u306f\u3058\u3081\u3068\u3059\u308b\u7d44\u7e54\u7279\u7570\u7684\u306a\u8ee2\u5199\u56e0\u5b50\u306e\u6a5f\u80fd\u3092\u7d71\u5408\u7684\u306b\u8abf\u7bc0\u3059\u308b\u65b0  \u898f\u306e\u8ee2\u5199\u5236\u5fa1\u69d8\u5f0f\u3092\u3053\u3053\u306b\u63d0\u5531\u3059\u308b\u3002\u79c1\u305f\u3061\u306e\u767a\u898b\u306f\u3001\u30d2\u30c8\u306b\u304a\u3044\u3066H3K36me3\u306e\u610f\u7fa9\u3092\u306f\u3058\u3081\u3066\u660e\u3089\u304b\u306b\u3057\u305f\u3060\u3051\u3067\u306a\u304f\u30014p\u75c7\u5019\u7fa4\u306e\u5206\u5b50\u75c5\u614b\u306e\u89e3\u660e\u306b\u3064\u306a\u304c\u308a\u3001\u3072\u3044\u3066\u306f\u3053\u306e\u75be\u60a3\u306e\u6cbb\u7642\u6cd5\u306e\u958b\u767a\u306b\u3082\u8ca2\u732e\u3059\u308b\u3053\u3068\u304c\u671f\u5f85\u3055\u308c\u308b\u3002<\/p>\n\n --><\/p>\n<p>Diverse histone modifications are catalyzed and   recognized by various specific proteins, establishing unique modification patterns that act as transcription signals. In particular, histone H3 trimethylation at lysine 36 (H3K36me3) is associated with actively transcribed regions and has been proposed to provide landmarks   for ongoing transcription; however, the control mechanisms and functions of H3K36me3 in higher eukaryotes are unknown. Here, we show that the H3K36me3-specific histone methyltransferase (HMTase) <u>W<\/u>olf-<u>H<\/u>irschhorn <u>s<\/u>yndrome <u>c<\/u>andidate 1 (WHSC1, also known as NSD2 or MMSET) functions in transcriptional regulation together with developmental transcription factors whose defects overlap with WHS human disease. We found that mouse Whsc1, one of five putative Set2 homologs, governed   H3K36me3 along euchromatin by associating with the cell type-specific transcription factors Sall1, Sall4, and Nanog in ES cells, and Nkx2-5 in embryonic hearts, regulating the expression of their target genes. Whsc1-deficient mice displayed growth retardation and various WHS-like midline defects, including congenital cardiovascular anomalies. The effects of <em>Whsc1<\/em> haploinsufficiency were increased in <em>Nkx2-5<\/em> heterozygous mutant hearts, indicating their functional link. We propose that WHSC1 functions together with developmental transcription   factors to prevent the inappropriate transcription that can lead to various pathophysiologies.<\/p>\n<p class=\"mt25\"><span class=\"lineFrame\">URL<\/span> <a href=\"http:\/\/www.med.osaka-u.ac.jp\/pub\/gts\/\" target=\"_blank\">http:\/\/www.med.osaka-u.ac.jp\/pub\/gts\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Click to enlarge Click to enlarge 2009-6-1 Publish Nature,460:287-91,2009 Diverse histone mod [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1808,"parent":462,"menu_order":180,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/657"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=657"}],"version-history":[{"count":9,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/657\/revisions"}],"predecessor-version":[{"id":2380,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/657\/revisions\/2380"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/462"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/1808"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=657"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}