23897429<\/a><\/a><\/p>\nAbstract<\/h2>\n
During adipocyte differentiation, significant epigenomic changes occur in association with the implementation of the adipogenic program. We have previously shown that histone acetylation increases during differentiation in a manner dependent on acetyl coenzyme A (acetyl-CoA) production by the enzyme ATP-citrate lyase (ACL). Whether ACL regulates nuclear targets in addition to histones during differentiation is not clear. In this study, we report that DNA methyltransferase 1 (DNMT1) levels in adipocytes are controlled in part by ACL and that silencing of DNMT1 can accelerate adipocyte differentiation. DNMT1 gene expression is induced early in 3T3-L1 adipocyte differentiation during mitotic clonal expansion and is critical for maintenance of DNA and histone H3K9 methylation patterns during this period. In the absence of DNMT1, adipocyte-specific gene expression and lipid accumulation occur precociously. Later in differentiation, DNMT1 levels decline in an ACL-dependent manner. ACL-mediated suppression of DNMT1 occurs at least in part by promoting expression of microRNA 148a (miR-148a), which represses DNMT1. Ectopic expression of miR-148a accelerates differentiation under standard conditions and can partially rescue a hypermethylation-mediated differentiation block. The data suggest a role for DNMT1 in modulating the timing of differentiation and describe a novel ACL-miR-148a-dependent mechanism for regulating DNMT1 during adipogenesis.<\/p><\/p>\n","protected":false},"excerpt":{"rendered":"
Londo\u00f1o Gentile T, Lu C, Lodato PM, Tse S, Olejniczak SH, Witze ES, Thompson CB, Wellen KE Mol. Cell. Biol. 2013 Oct;33(19):3864-78 PMID: 23897429 Abstract During adipocyte differentiation, significant epigenomic changes occur in association with the implementation of the adipogenic program. We have previously shown that histone acetylation increases during differentiation in a manner dependent<\/p>\n
Continue reading DNMT1 is regulated by ATP-citrate lyase and maintains methylation patterns during adipocyte differentiation<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[41],"tags":[],"class_list":["post-10354","post","type-post","status-publish","format-standard","hentry","category-ireach"],"acf":[],"_links":{"self":[{"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/posts\/10354","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/comments?post=10354"}],"version-history":[{"count":0,"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/posts\/10354\/revisions"}],"wp:attachment":[{"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/media?parent=10354"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/categories?post=10354"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/research.christianacare.org\/publications\/wp-json\/wp\/v2\/tags?post=10354"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}