NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

Beiying Qiu, Xiaohe Shi, Ee Tsin Wong, Joy Lim, Marco Bezzi, Diana Low, Qiling Zhou, Semih Can Akincilar, Manikandan Lakshmanan, Hannah L.F. Swa, Jill Mae Lan Tham, Jayantha Gunaratne, King Yip Cheng, Wanjin Hong, Karen S.L. Lam, Masahito Ikawa, Ernesto Guccione, Aimin Xu, Weiping Han, Vinay Tergaonkar

Research output: Journal article publicationJournal articleAcademic researchpeer-review

24 Citations (Scopus)

Abstract

Although much is known about the molecular players in insulin signaling, there is scant information about transcriptional regulation of its key components. We now find that NUCKS is a transcriptional regulator of the insulin signaling components, including the insulin receptor (IR). Knockdown of NUCKS leads to impaired insulin signaling in endocrine cells. NUCKS knockout mice exhibit decreased insulin signaling and increased body weight/fat mass along with impaired glucose tolerance and reduced insulin sensitivity, all of which are further exacerbated by a high-fat diet (HFD). Genome-wide ChIP-seq identifies metabolism and insulin signaling as NUCKS targets. Importantly, NUCKS is downregulated in individuals with a high body mass index and in HFD-fed mice, and conversely, its levels increase upon starvation. Altogether, NUCKS is a physiological regulator of energy homeostasis and glucose metabolism that works by regulating chromatin accessibility and RNA polymerase II recruitment to the promoters of IR and other insulin pathway modulators.
Original languageEnglish
Pages (from-to)1876-1886
Number of pages11
JournalCell Reports
Volume7
Issue number6
DOIs
Publication statusPublished - 26 Jun 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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