NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling
Title:
NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling
Other Titles:
Cell Reports
Keywords:
Publication Date:
26 June 2014
Citation:
NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling Qiu, Beiying et al. Cell Reports , Volume 7 , Issue 6 , 1876 - 1886
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
Description:
ISSN:
2211-1247
Files uploaded: