Newswise \u2014 CLEVELAND\u2014Shedding light on what determines how cells become what they are meant to be\u2014nerves, bone, muscles, etc.\u2014can also help researchers understand how diseases develop when these biological programs break down.<\/p>\n
Now, researchers at Case Western Reserve University<\/a> have discovered a key synergistic role for two epigenetic markers\u2014molecules that help tell genes to turn on and off\u2014involved in programming cell fate. Importantly, turning off these two markers causes genes to over-activate, disrupting normal cell development.<\/p>\n The research is published in the journal Science Advances<\/a>. The findings have importance for understanding neurodevelopmental diseases and may indicate a new target for treating some types of leukemia with drugs already in clinical trials for treating other cancers.<\/p>\n \u201cNo one understood how these markers worked together, and now we have a mechanism,\u201d said principal investigator Kaixiang Cao<\/a>, an assistant professor of biochemistry and genetics and genome sciences at the Case Western Reserve School of Medicine<\/a> and a member of the Case Comprehensive Cancer Center<\/a>. \u201cNot only that, but we also think there could be a therapeutic impact.\u201d<\/p>\n Epigenetic mechanisms play a central role in regulating cell fate during normal development and in disease. Deciphering these mechanisms shed light on developing novel therapies for treating human developmental syndromes and cancer.<\/p>\n In model organism stem cells, the research team used cutting-edge genetic engineering to remove the enzymes responsible for adding epigenetic markers called H3K79 methylation and H3K36 trimethylation\u2014one at a time and together. They discovered that removing either mark alone caused only minor changes, but losing both at once sent gene activity into overdrive and blocked the cells\u2019 ability to become neurons.<\/p>\n \u201cTo our surprise, when we removed the markers, we found that the genes were over-activated,\u201d said Cheng Zeng<\/a>, a CWRU graduate student who contributed significantly to this study and received his PhD in biochemistry this month from the medical school. \u201cWhen people have looked at these markers individually, it seemed as though they were involved in turning genes on, so removing them was thought to turn the genes off. It was actually the opposite.\u201d<\/p>\n While these markers are implicated in rare neurodevelopmental diseases, they are more prevalent in cancer, said Cao, who cited Case Western Reserve\u2019s collaborative research culture and support for team\u2019s promising findings.<\/p>\n In leukemia, a cancer of the blood, defects in methylation may cause blood stem cells to fail to differentiate properly into mature red and white blood cells. The study identified a potential new treatment strategy: blocking a protein partnership (YAP-TEAD) that becomes overactive when both methylation marks are missing.<\/p>\n In a specific cohort of patients carrying a misregulation in both epigenetic marks, Cao said treatment targeting the YAP-TEAD pathway might prove successful.<\/p>\n Drugs targeting the YAP-TEAD pathway are already in clinical trials for treating other types of cancers, like mesothelioma (a type of cancer that affects the lining of the lungs or abdomen). These drugs were not previously considered for treating leukemia having abnormal methylation.<\/p>\n The hypothesis would have to first be tested in clinical models of the disease before moving to human trials.<\/p>\n Collaborators on the research include: Fulai Jin<\/a>, a professor in genetics and genome sciences at the medical school and co-leader of the cancer genomics and epigenomics program at the Case Comprehensive Cancer Center; CWRU biochemistry research assistant Emmalee Cooke; and researchers at Fudan University in Shanghai. The research was supported by the U.S. National Institutes of Health.\u00a0<\/p>\n \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 ###<\/p>\n At Case Western Reserve, one of the nation’s leading research universities, we’re driven to seek knowledge and find solutions to some of the world’s most pressing problems. Nearly 6,200 undergraduate and 6,100 graduate students from across 96 countries study in our more than 250 degree programs across arts, dental medicine, engineering, law, management, medicine, nursing, science and social work. Our location in Cleveland, Ohio\u2014a hub of cultural, business and healthcare activity\u2014gives students unparalleled access to engaging academic, research, clinical, entrepreneurial and volunteer opportunities and prepares them to join our network of 125,000+ alumni making an impact worldwide. Visit\u00a0case.edu<\/a>\u00a0to learn more.<\/p>\n \u00a0<\/p>\n \u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"Newswise \u2014 CLEVELAND\u2014Shedding light on what determines how cells become what they are meant to be\u2014nerves, bone, muscles,…\n","protected":false},"author":2,"featured_media":70499,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[6810,7992,2768,49,48,7714,44120,20814,3184,44119,316,23749,6808,66,7822],"class_list":["post-70498","post","type-post","status-publish","format-standard","has-post-thumbnail","category-genetics","tag-all-journal-news","tag-biotech","tag-blood","tag-ca","tag-canada","tag-cancer","tag-case-western-reserve-university","tag-cell-biology","tag-clinical-trials","tag-epigeneticsgene-controlcancerleukemianeurodevelopmentepigenomics","tag-genetics","tag-neuro","tag-newswise","tag-science","tag-stem-cells"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/70498","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/comments?post=70498"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/70498\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media\/70499"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media?parent=70498"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/categories?post=70498"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/tags?post=70498"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}