Hepatocyte nuclear factor 4alpha coordinates a transcription factor network regulating hepatic fatty acid metabolism.

Molecular and Cellular Biology
Celia Pilar Martinez-JimenezIannis Talianidis

Abstract

Adaptation of liver to nutritional signals is regulated by several transcription factors that are modulated by intracellular metabolites. Here, we demonstrate a transcription factor network under the control of hepatocyte nuclear factor 4alpha (HNF4alpha) that coordinates the reciprocal expression of fatty acid transport and metabolizing enzymes during fasting and feeding conditions. Hes6 is identified as a novel HNF4alpha target, which in normally fed animals, together with HNF4alpha, maintains PPARgamma expression at low levels and represses several PPARalpha-regulated genes. During fasting, Hes6 expression is diminished, and peroxisome proliferator-activated receptor alpha (PPARalpha) replaces the HNF4alpha/Hes6 complex on regulatory regions of target genes to activate transcription. Gene expression and promoter occupancy analyses confirmed that HNF4alpha is a direct activator of the Pparalpha gene in vivo and that its expression is subject to feedback regulation by PPARalpha and Hes6 proteins. These results establish the fundamental role of dynamic regulatory interactions between HNF4alpha, Hes6, PPARalpha, and PPARgamma in the coordinated expression of genes involved in fatty acid transport and metabolism.

References

May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J AytéF G Hegardt
May 15, 1994·Genes & Development·P TontonozB M Spiegelman
Feb 15, 1997·European Journal of Biochemistry·J D McGarry, N F Brown
Jun 8, 1999·The Journal of Clinical Investigation·S KerstenW Wahli
Jul 6, 2000·Molecular Cell·E SoutoglouI Talianidis
Oct 5, 2001·Molecular and Cellular Biology·P Hatzis, I Talianidis
May 8, 2002·The Journal of Clinical Investigation·Jay D HortonMichael S Brown
Jun 29, 2002·Cellular and Molecular Life Sciences : CMLS·A K HihiW Wahli
Dec 31, 2002·Molecular Cell·Pantelis Hatzis, Iannis Talianidis
Mar 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·James RheeBruce M Spiegelman
Sep 16, 2003·Molecular and Cellular Biology·Michel-Olivier GrattonStefano Stifani
Oct 30, 2003·The Journal of Biological Chemistry·Yusuke InoueFrank J Gonzalez
Apr 22, 2004·Molecular Cell·Antigone KouskoutiIannis Talianidis
Dec 24, 2004·The EMBO Journal·Antigone Kouskouti, Iannis Talianidis
Jun 24, 2005·The EMBO Journal·Konstantinos BouliasIannis Talianidis
Nov 3, 2005·Journal of Lipid Research·Yusuke InoueFrank J Gonzalez
Feb 8, 2006·Annual Review of Physiology·Nada Y Kalaany, David J Mangelsdorf
Apr 8, 2006·Physiological Reviews·Béatrice DesvergneWalter Wahli
Nov 30, 2006·Pharmacological Reviews·Liliane MichalikWalter Wahli
Apr 9, 2008·Cell Metabolism·Kimihiko MatsusueFrank J Gonzalez
Jun 4, 2008·Annual Review of Biochemistry·Peter Tontonoz, Bruce M Spiegelman
Aug 30, 2008·Molecular Cell·Antonis TatarakisIannis Talianidis
Sep 3, 2008·Cell Metabolism·Ulrike LemkeStephan Herzig
Jan 31, 2009·Molecular Endocrinology·Xuefen XieFrances M Sladek
Mar 4, 2009·Cell Metabolism·Laura PalankerCarl S Thummel

❮ Previous
Next ❯

Citations

May 19, 2012·Nature Reviews. Genetics·Johan Holmberg, Thomas Perlmann
Dec 15, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anca D PetrescuFriedhelm Schroeder
Jan 21, 2012·BMC Genomics·Janice S LeeJ Christopher Corton
Aug 24, 2013·PloS One·Maria KonstandiFrank J Gonzalez
Jun 12, 2013·Biochimica Et Biophysica Acta·Anca D PetrescuFriedhelm Schroeder
May 13, 2014·Biochimica Et Biophysica Acta·Panagiota Karagianni, Iannis Talianidis
Oct 16, 2015·Nature Reviews. Genetics·Adelheid LempradlJosef M Penninger
Jun 20, 2015·Cellular and Molecular Life Sciences : CMLS·Carmen Berasain, Matías A Avila
May 16, 2015·Molecular Biology and Evolution·Shan Li, Ivan Ovcharenko
Jul 15, 2015·Infectious Agents and Cancer·Zhao WangAjit Kumar
Nov 22, 2014·Nucleic Acids Research·Luke NortonSami Heikkinen
Aug 21, 2014·PloS One·Samuel RommelaerePhilippe Naquet
Sep 12, 2016·Canadian Journal of Diabetes·Emayavaramban Priyadarshini, Carani Venkatraman Anuradha
Jul 4, 2012·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·John DoelmanJohn P Cant
Feb 16, 2018·Journal of Virology·Savvina MoustafaPenelope Mavromara
Sep 17, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Seong Chul KimYoon Kwang Lee
Mar 7, 2018·Hepatology Communications·Eduardo H GilglioniRonald P J Oude Elferink
Jun 24, 2019·The FEBS Journal·Maria KonstandiFrank J Gonzalez
Apr 27, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Miaoran Ning, Hyunyoung Jeong
Nov 15, 2013·Advances in Nutrition·Douglas G Mashek
May 8, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Bharat BhushanGeorge K Michalopoulos
Nov 7, 2019·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Dovydas GecysVaiva Lesauskaite
Apr 3, 2020·Journal of Clinical Medicine·Sarthak SahooMohit Kumar Jolly
Mar 31, 2015·Endocrinology·Risheng YePhilipp E Scherer
May 7, 2015·Molecular Pharmacology·Xian Pan, Hyunyoung Jeong
Feb 7, 2017·The Journal of Clinical Investigation·Zhu WangDavid J Mangelsdorf
Oct 21, 2018·Nature Communications·Baharan FekryKristin Eckel-Mahan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.