Crystal structures reveal a new and novel FoxO1 binding site within the human glucose-6-phosphatase catalytic subunit 1 gene promoter

Singh, Puja; Han, Eun Hee; Endrizzi, James A.; O'Brien, Richard M.; Chi, Young-In

doi:10.1016/j.jsb.2017.02.006

Crystal structures reveal a new and novel FoxO1 binding site within the human glucose-6-phosphatase catalytic subunit 1 gene promoter

Journal Article · Mon Feb 20 00:00:00 EST 2017 · Journal of Structural Biology

DOI:https://doi.org/10.1016/j.jsb.2017.02.006· OSTI ID:1357623

Singh, Puja ^[1]; Han, Eun Hee ^[2]; Endrizzi, James A. ^[3]; O'Brien, Richard M. ^[4]; Chi, Young-In ^[1]

Univ. of Minnesota, Austin, MN (United States)
Univ. of Minnesota, Austin, MN (United States); Korea Basic Science Inst., Daejeon (Republic of Korea)
Univ. of Minnesota, Austin, MN (United States); SuperNova C LLC, Missoula, MT (United States)
Vanderbilt Univ. School of Medicine, Nashville, TN (United States)

Human glucose-6-phosphatase plays a vital role in blood glucose homeostasis and holds promise as a therapeutic target for diabetes. Expression of its catalytic subunit gene 1 (G6PC1) is tightly regulated by metabolic-response transcription factors such as FoxO1 and CREB. Although at least three potential FoxO1 binding sites (insulin response elements, IREs) and one CREB binding site (cAMP response element, CRE) within the proximal region of the G6PC1 promoter have been identified, the interplay between FoxO1 and CREB and between FoxO1 bound at multiple IREs has not been well characterized. Here we present the crystal structures of the FoxO1 DNA binding domain in complex with the G6PC1 promoter. Here, these complexes reveal the presence of a new non-consensus FoxO1 binding site that overlaps the CRE, suggesting a mutual exclusion mechanism for FoxO1 and CREB binding at the G6PC1 promoter. Additional findings include (i) non-canonical FoxO1 recognition sites, (ii) incomplete FoxO1 occupancies at the available IRE sites, and (iii) FoxO1 dimeric interactions that may play a role in stabilizing DNA looping. These findings provide insight into the regulation of G6PC1 gene transcription by FoxO1, and demonstrate a high versatility of target gene recognition by FoxO1 that correlates with its diverse roles in biology.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: American Diabetes Assoc.; Commonwealth of Kentucky Diabetes Research Trust Fund; National Inst. of Health

OSTI ID:: 1357623

Journal Information:: Journal of Structural Biology, Journal Name: Journal of Structural Biology Journal Issue: 1 Vol. 198; ISSN 1047-8477

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (58)

FoxO1: A molecule for all seasons Kousteni, Stavroula Journal of Bone and Mineral Research, Vol. 26, Issue 5 https://doi.org/10.1002/jbmr.306	journal	May 2011
The grammar of transcriptional regulation Weingarten-Gabbay, Shira; Segal, Eran Human Genetics, Vol. 133, Issue 6 https://doi.org/10.1007/s00439-013-1413-1	journal	January 2014
The role of FOXO in the regulation of metabolism Gross, Danielle N.; Wan, Min; Birnbaum, Morris J. Current Diabetes Reports, Vol. 9, Issue 3 https://doi.org/10.1007/s11892-009-0034-5	journal	May 2009
Transcriptional regulators of hepatic gluconeogenesis Oh, Kyoung-Jin; Han, Hye-Sook; Kim, Min-Jung Archives of Pharmacal Research, Vol. 36, Issue 2 https://doi.org/10.1007/s12272-013-0018-5	journal	January 2013
The SLC37 Family of Sugar-Phosphate/Phosphate Exchangers Chou, Janice Y.; Mansfield, Brian C. Current Topics in Membranes https://doi.org/10.1016/B978-0-12-800223-0.00010-4	book	January 2014
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Enhanceosomes Merika, Menie; Thanos, Dimitris Current Opinion in Genetics & Development, Vol. 11, Issue 2 https://doi.org/10.1016/S0959-437X(00)00180-5	journal	April 2001
Hepatic glucose metabolism in humans—its role in health and disease Roden, Michael; Bernroider, Elisabeth Best Practice & Research Clinical Endocrinology & Metabolism, Vol. 17, Issue 3 https://doi.org/10.1016/S1521-690X(03)00031-9	journal	September 2003
Multiple modes of chromatin remodeling by Forkhead box proteins Lalmansingh, Avin S.; Karmakar, Sudipan; Jin, Yetao Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Vol. 1819, Issue 7 https://doi.org/10.1016/j.bbagrm.2012.02.018	journal	July 2012
Structural basis for DNA recognition by FOXO proteins Obsil, Tomas; Obsilova, Veronika Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1813, Issue 11 https://doi.org/10.1016/j.bbamcr.2010.11.025	journal	November 2011
Role of resveratrol in FOXO1-mediated gluconeogenic gene expression in the liver Park, Joo-Man; Kim, Tae-Hyun; Bae, Jin-Sik Biochemical and Biophysical Research Communications, Vol. 403, Issue 3-4 https://doi.org/10.1016/j.bbrc.2010.11.028	journal	December 2010
Class IIa Histone Deacetylases Are Hormone-Activated Regulators of FOXO and Mammalian Glucose Homeostasis Mihaylova, Maria M.; Vasquez, Debbie S.; Ravnskjaer, Kim Cell, Vol. 145, Issue 4 https://doi.org/10.1016/j.cell.2011.03.043	journal	May 2011
Impaired Regulation of Hepatic Glucose Production in Mice Lacking the Forkhead Transcription Factor Foxo1 in Liver Matsumoto, Michihiro; Pocai, Alessandro; Rossetti, Luciano Cell Metabolism, Vol. 6, Issue 3 https://doi.org/10.1016/j.cmet.2007.08.006	journal	September 2007
OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen Trends in Molecular Medicine, Vol. 14, Issue 5 https://doi.org/10.1016/j.molmed.2008.03.002	journal	May 2008
The enhanceosome Panne, Daniel Current Opinion in Structural Biology, Vol. 18, Issue 2 https://doi.org/10.1016/j.sbi.2007.12.002	journal	April 2008
Structural Basis for DNA Recognition by FoxO1 and Its Regulation by Posttranslational Modification Brent, Michael M.; Anand, Ruchi; Marmorstein, Ronen Structure, Vol. 16, Issue 9 https://doi.org/10.1016/j.str.2008.06.013	journal	September 2008
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1 Herzig, Stephan; Long, Fanxin; Jhala, Ulupi S. Nature, Vol. 413, Issue 6852 https://doi.org/10.1038/35093131	journal	September 2001
A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange Liu, Yi; Dentin, Renaud; Chen, Danica Nature, Vol. 456, Issue 7219 https://doi.org/10.1038/nature07349	journal	October 2008
The long-range interaction landscape of gene promoters Sanyal, Amartya; Lajoie, Bryan R.; Jain, Gaurav Nature, Vol. 489, Issue 7414 https://doi.org/10.1038/nature11279	journal	September 2012
Integrated control of hepatic lipogenesis versus glucose production requires FoxO transcription factors Haeusler, Rebecca A.; Hartil, Kirsten; Vaitheesvaran, Bhavapriya Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms6190	journal	October 2014
Dynamic regulation of transcriptional states by chromatin and transcription factors Voss, Ty C.; Hager, Gordon L. Nature Reviews Genetics, Vol. 15, Issue 2 https://doi.org/10.1038/nrg3623	journal	December 2013
Structure/function relationships underlying regulation of FOXO transcription factors Obsil, T.; Obsilova, V. Oncogene, Vol. 27, Issue 16 https://doi.org/10.1038/onc.2008.20	journal	April 2008
The FoxO code Calnan, D. R.; Brunet, A. Oncogene, Vol. 27, Issue 16 https://doi.org/10.1038/onc.2008.21	journal	April 2008
The role of FoxO in the regulation of metabolism Gross, D. N.; van den Heuvel, A. P. J.; Birnbaum, M. J. Oncogene, Vol. 27, Issue 16 https://doi.org/10.1038/onc.2008.25	journal	April 2008
FOXO animal models reveal a variety of diverse roles for FOXO transcription factors Arden, K. C. Oncogene, Vol. 27, Issue 16 https://doi.org/10.1038/onc.2008.27	journal	April 2008
Insulin and epidermal growth factor suppress basal glucose-6-phosphatase catalytic subunit gene transcription through overlapping but distinct mechanisms Onuma, Hiroshi; Oeser, James K.; Nelson, Bryce A. Biochemical Journal, Vol. 417, Issue 2 https://doi.org/10.1042/BJ20080999	journal	December 2008
Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues Furuyama, Tatsuo; Nakazawa, Toru; Nakano, Itsuko Biochemical Journal, Vol. 349, Issue 2 https://doi.org/10.1042/bj3490629	journal	July 2000
Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification Hosaka, T.; Biggs, W. H.; Tieu, D. Proceedings of the National Academy of Sciences, Vol. 101, Issue 9 https://doi.org/10.1073/pnas.0400093101	journal	February 2004
Transcription factors mediate long-range enhancer-promoter interactions Nolis, I. K.; McKay, D. J.; Mantouvalou, E. Proceedings of the National Academy of Sciences, Vol. 106, Issue 48 https://doi.org/10.1073/pnas.0902454106	journal	November 2009
Differential Role of Hepatocyte Nuclear Factor-1 in the Regulation of Glucose-6-phosphatase Catalytic Subunit Gene Transcription by cAMP in Liver- and Kidney-derived Cell Lines Streeper, Ryan S.; Svitek, Christina A.; Goldman, Joshua K. Journal of Biological Chemistry, Vol. 275, Issue 16 https://doi.org/10.1074/jbc.275.16.12108	journal	April 2000
FoxOs Function Synergistically to Promote Glucose Production Haeusler, Rebecca A.; Kaestner, Klaus H.; Accili, Domenico Journal of Biological Chemistry, Vol. 285, Issue 46 https://doi.org/10.1074/jbc.C110.175851	journal	November 2010
AMPK-dependent Repression of Hepatic Gluconeogenesis via Disruption of CREB·CRTC2 Complex by Orphan Nuclear Receptor Small Heterodimer Partner Lee, Ji-Min; Seo, Woo-Young; Song, Kwang-Hoon Journal of Biological Chemistry, Vol. 285, Issue 42 https://doi.org/10.1074/jbc.M110.134890	journal	October 2010
Loss of Interdependent Binding by the FoxO1 and FoxA1/A2 Forkhead Transcription Factors Culminates in Perturbation of Active Chromatin Marks and Binding of Transcriptional Regulators at Insulin-sensitive Genes Yalley, Akua; Schill, Daniel; Hatta, Mitsutoki Journal of Biological Chemistry, Vol. 291, Issue 16 https://doi.org/10.1074/jbc.M115.677583	journal	April 2016
The Three Insulin Response Sequences in the Glucose-6-phosphatase Catalytic Subunit Gene Promoter Are Functionally Distinct Vander Kooi, Beth T.; Streeper, Ryan S.; Svitek, Christina A. Journal of Biological Chemistry, Vol. 278, Issue 14 https://doi.org/10.1074/jbc.M212570200	journal	April 2003
A Combination of HNF-4 and Foxo1 Is Required for Reciprocal Transcriptional Regulation of Glucokinase and Glucose-6-phosphatase Genes in Response to Fasting and Feeding Hirota, Keiko; Sakamaki, Jun-ichi; Ishida, Junji Journal of Biological Chemistry, Vol. 283, Issue 47 https://doi.org/10.1074/jbc.M806179200	journal	November 2008
Glucose-6-phosphatase Catalytic Subunit Gene Family Hutton, John C.; O'Brien, Richard M. Journal of Biological Chemistry, Vol. 284, Issue 43 https://doi.org/10.1074/jbc.R109.025544	journal	October 2009
Evolutionary Origins of Transcription Factor Binding Site Clusters He, Xin; Duque, Thyago S. P. C.; Sinha, Saurabh Molecular Biology and Evolution, Vol. 29, Issue 3 https://doi.org/10.1093/molbev/msr277	journal	November 2011
Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification Tsai, K. -L.; Sun, Y. -J.; Huang, C. -Y. Nucleic Acids Research, Vol. 35, Issue 20 https://doi.org/10.1093/nar/gkm703	journal	November 2007
Conformational analysis of nucleic acids revisited: Curves+ Lavery, R.; Moakher, M.; Maddocks, J. H. Nucleic Acids Research, Vol. 37, Issue 17 https://doi.org/10.1093/nar/gkp608	journal	July 2009
Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development Kazemian, Majid; Pham, Hannah; Wolfe, Scot A. Nucleic Acids Research, Vol. 41, Issue 17 https://doi.org/10.1093/nar/gkt598	journal	July 2013
Unified nomenclature for the winged helix/forkhead transcription factors Kaestner, Klaus H.; Knöchel, Walter; Martínez, Daniel E. Genes & Development, Vol. 14, Issue 2 https://doi.org/10.1101/gad.14.2.142	journal	January 2000
Homotypic clusters of transcription factor binding sites are a key component of human promoters and enhancers Gotea, V.; Visel, A.; Westlund, J. M. Genome Research, Vol. 20, Issue 5 https://doi.org/10.1101/gr.104471.109	journal	April 2010
Sparse matrix sampling: a screening method for crystallization of proteins Jancarik, J.; Kim, S. H. Journal of Applied Crystallography, Vol. 24, Issue 4 https://doi.org/10.1107/S0021889891004430	journal	August 1991
MOLREP an Automated Program for Molecular Replacement Vagin, A.; Teplyakov, A. Journal of Applied Crystallography, Vol. 30, Issue 6, p. 1022-1025 https://doi.org/10.1107/S0021889897006766	journal	December 1997
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Discovery of Novel Forkhead Box O1 Inhibitors for Treating Type 2 Diabetes: Improvement of Fasting Glycemia in Diabetic db/db Mice Nagashima, Takeyuki; Shigematsu, Nobuharu; Maruki, Riyo Molecular Pharmacology, Vol. 78, Issue 5 https://doi.org/10.1124/mol.110.065714	journal	August 2010
Regulation of Glucose Production by the Liver Nordlie, Robert C.; Foster, James D.; Lange, Alex J. Annual Review of Nutrition, Vol. 19, Issue 1 https://doi.org/10.1146/annurev.nutr.19.1.379	journal	July 1999
Selective stimulation of G-6-Pase catalytic subunit but not G-6- P transporter gene expression by glucagon in vivo and cAMP in situ Hornbuckle, Lauri A.; Everett, Carrie A.; Martin, Cyrus C. American Journal of Physiology-Endocrinology and Metabolism, Vol. 286, Issue 5 https://doi.org/10.1152/ajpendo.00455.2003	journal	May 2004
FoxO gene family evolution in vertebrates Wang, Minghui; Zhang, Xiangzhe; Zhao, Hongbo BMC Evolutionary Biology, Vol. 9, Issue 1 https://doi.org/10.1186/1471-2148-9-222	journal	January 2009
The Glucose-6-Phosphatase Catalytic Subunit Gene Promoter Contains Both Positive and Negative Glucocorticoid Response Elements Vander Kooi, Beth T.; Onuma, Hiroshi; Oeser, James K. Molecular Endocrinology, Vol. 19, Issue 12 https://doi.org/10.1210/me.2004-0497	journal	December 2005
Correlation between FOXO1a (FKHR) and FOXO3a (FKHRL1) Binding and the Inhibition of Basal Glucose-6-Phosphatase Catalytic Subunit Gene Transcription by Insulin Onuma, Hiroshi; Vander Kooi, Beth T.; Boustead, Jared N. Molecular Endocrinology, Vol. 20, Issue 11 https://doi.org/10.1210/me.2006-0085	journal	November 2006
Dynamic FoxO transcription factors Huang, Haojie; Tindall, Donald J. Journal of Cell Science, Vol. 120, Issue 15 https://doi.org/10.1242/jcs.001222	journal	August 2007
FoxO1 Inhibitors: The Future Medicine for Metabolic Disorders? Pandey, Anuradha; Santosh Kumar, Goru; Kadakol, Almesh Current Diabetes Reviews, Vol. 12, Issue 3 https://doi.org/10.2174/1573399811666150804104858	journal	July 2016
Targeting Foxo1 in Mice Using Antisense Oligonucleotide Improves Hepatic and Peripheral Insulin Action Samuel, V. T.; Choi, C. S.; Phillips, T. G. Diabetes, Vol. 55, Issue 7 https://doi.org/10.2337/db05-0705	journal	June 2006
FoxO6 Integrates Insulin Signaling With Gluconeogenesis in the Liver Kim, Dae Hyun; Perdomo, German; Zhang, Ting Diabetes, Vol. 60, Issue 11 https://doi.org/10.2337/db11-0548	journal	September 2011
CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis Oh, Kyoung-Jin; Han, Hye-Sook; Kim, Min-Jung BMB Reports, Vol. 46, Issue 12 https://doi.org/10.5483/BMBRep.2013.46.12.248	journal	December 2013

Cited By (5)

Cannabinoid receptor 1 knockout alleviates hepatic steatosis by downregulating perilipin 2 Irungbam, Karuna; Churin, Yuri; Matono, Tomomitsu Laboratory Investigation, Vol. 100, Issue 3 https://doi.org/10.1038/s41374-019-0327-5	journal	September 2019
Structural basis for DNA recognition by FOXC2 Chen, Xiaojuan; Wei, Hudie; Li, Jun Nucleic Acids Research, Vol. 47, Issue 7 https://doi.org/10.1093/nar/gkz077	journal	February 2019
AMPK and AKT protein kinases hierarchically phosphorylate the N-terminus of the FOXO1 transcription factor, modulating interactions with 14-3-3 proteins Saline, Maria; Badertscher, Lukas; Wolter, Madita Journal of Biological Chemistry, Vol. 294, Issue 35 https://doi.org/10.1074/jbc.ra119.008649	journal	July 2019
DNA-mediated dimerization on a compact sequence signature controls enhancer engagement and regulation by FOXA1 Wang, Xuecong; Srivastava, Yogesh; Jankowski, Aleksander Nucleic Acids Research, Vol. 46, Issue 11 https://doi.org/10.1093/nar/gky259	journal	April 2018
AMPK and AKT protein kinases hierarchically phosphorylate the N-terminus of the FOXO1 transcription factor, modulating interactions with 14-3-3 proteins Saline, Maria; Badertscher, Lukas; Wolter, Madita Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2019-02892	text	January 2019

Similar Records

c-Jun represses the human insulin promoter activity that depends on multiple cAMP response elements

Journal Article · Fri Jan 31 23:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States) · OSTI ID:5688665

Glucose Regulates the Expression of the Apolipoprotein A5 Gene

Journal Article · Mon Apr 07 00:00:00 EDT 2008 · Journal of Molecular Biology · OSTI ID:936098

Sp1 and CREB regulate basal transcription of the human SNF2L gene

Journal Article · Fri Apr 04 00:00:00 EDT 2008 · Biochemical and Biophysical Research Communications · OSTI ID:21043691

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CREB
Crystal structure
FoxO1
Gene regulation
Gluconeogenesis
Glucose-6-phosphatase
Protein-DNA interaction

Crystal structures reveal a new and novel FoxO1 binding site within the human glucose-6-phosphatase catalytic subunit 1 gene promoter

Citation Formats

References (58)

Cited By (5)

Similar Records

Related Subjects