0 83

Cited 0 times in

Zbtb7c is a critical gluconeogenic transcription factor that induces glucose-6-phosphatase and phosphoenylpyruvate carboxykinase 1 genes expression during mice fasting

Authors
 Won-Il Choi  ;  Jae-Hyeon Yoon  ;  Ji-Yang Song  ;  Bu-Nam Jeon  ;  Joo-Man Park  ;  Dong-In Koh  ;  Yong-ho Ahn  ;  Kyung-Sup Kim  ;  In-Kyu Lee  ;  Man-Wook Hur 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, Vol.1862(6) : 643-656, 2019 
Journal Title
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 
ISSN
 1874-9399 
Issue Date
2019
Keywords
Foxo1 ; G6pc ; Gluconeogenesis ; Hdac3 ; Pck1 ; Zbtb7c
Abstract
Gluconeogenesis is essential for blood glucose homeostasis during fasting and is regulated by various enzymes, which are encoded by gluconeogenic genes. Those genes are controlled by various transcription factors. Zinc finger and BTB domain-containing 7c (Zbtb7c, also called Kr-pok) is a BTB-POZ family transcription factor with proto-oncogenic activity. Previous findings have indicated that Zbtb7c is involved in the regulation of fatty acid biosynthesis, suggesting an involvement also in primary metabolism. We found here that fasting induced Zbtb7c expression in the mouse liver and in primary liver hepatocytes. We also observed that Zbtb7c-knockout mice have decreased blood glucose levels, so we investigated whether Zbtb7c plays a role in gluconeogenesis. Indeed, differential gene expression analysis of Zbtb7c-knockout versus wild type mouse livers showed downregulated transcription of gluconeogenic genes encoding the glucose 6-phosphatase catalytic subunit (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1), while Zbtb7c expression upregulated these two genes, under fasting conditions. Mechanistically, we found that when complexed with histone deacetylase 3 (Hdac3), Zbtb7c binds insulin response elements (IREs) within the G6pc and Pck1 promoters. Moreover, complexed Zbtb7c deacetylated forkhead box O1 (Foxo1), thereby increasing Foxo1 binding to the G6pc and Pck1 IREs, resulting in their transcriptional activation. These results demonstrate Zbtb7c to be a crucial metabolic regulator of blood glucose homeostasis, during mammalian fasting.
Full Text
https://www.sciencedirect.com/science/article/pii/S1874939918305182
DOI
10.1016/j.bbagrm.2019.04.001
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Jeon, Bu Nam(전부남)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/169873
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse