Liver-Specific Hepatocyte Nuclear Factor-4α Deficiency: Greater Impact on Gene Expression in Male than in Female Mouse Liver

Sladek FM 1994Orphan receptor HNF-4 and liver-specific gene expression.Receptor4:64

Lemaigre F, Zaret KS 2004Liver development update: new embryo models, cell lineage control, and morphogenesis.Curr Opin Genet Dev14:582–590

Li J, Ning G, Duncan SA 2000Mammalian hepatocyte differentiation requires the transcription factor HNF-4α.Genes Dev14:464–474

Costa RH, Kalinichenko VV, Holterman AX, Wang X 2003Transcription factors in liver development, differentiation, and regeneration.Hepatology38:1331–1347

Wiwi CA, Waxman DJ 2004Role of hepatocyte nuclear factors in growth hormone-regulated, sexually dimorphic expression of liver cytochromes P450.Growth Factors22:79–88

Cheung C, Akiyama TE, Kudo G, Gonzalez FJ 2003Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-α (HNF1α)-deficient mice.Biochem Pharmacol66:2011–2020

Clotman F, Lannoy VJ, Reber M, Cereghini S, Cassiman D, Jacquemin P, Roskams T, Rousseau GG, Lemaigre FP 2002The onecut transcription factor HNF6 is required for normal development of the biliary tract.Development129:1819–1828

Shih DQ, Navas MA, Kuwajima S, Duncan SA, Stoffel M 1999Impaired glucose homeostasis and neonatal mortality in hepatocyte nuclear factor 3α-deficient mice.Proc Natl Acad Sci USA96:10152–10157

Wang ND, Finegold MJ, Bradley A, Ou CN, Abdelsayed SV, Wilde MD, Taylor LR, Wilson DR, Darlington GJ 1995Impaired energy homeostasis in C/EBPα knockout mice.Science269:1108–1112

Chen WS, Manova K, Weinstein DC, Duncan SA, Plump AS, Prezioso VR, Bachvarova RF, Darnell Jr JE 1994Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.Genes Dev8:2466–2477

Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ 2001Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis.Mol Cell Biol21:1393–1403

Hanniman EA, Lambert G, Inoue Y, Gonzalez FJ, Sinal CJ 2006Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4α, and PGC-1α.J Lipid Res47:2503–2514

Inoue Y, Yu AM, Yim SH, Ma X, Krausz KW, Inoue J, Xiang CC, Brownstein MJ, Eggertsen G, Bjorkhem I, Gonzalez FJ 2006Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4α.J Lipid Res47:215–227

Miura A, Yamagata K, Kakei M, Hatakeyama H, Takahashi N, Fukui K, Nammo T, Yoneda K, Inoue Y, Sladek FM, Magnuson MA, Kasai H, Miyagawa J, Gonzalez FJ, Shimomura I 2006Hepatocyte nuclear factor-4α is essential for glucose-stimulated insulin secretion by pancreatic β-cells.J Biol Chem281:5246–5257

Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, MacIsaac KD, Rolfe PA, Conboy CM, Gifford DK, Fraenkel E 2007Tissue-specific transcriptional regulation has diverged significantly between human and mouse.Nat Genet39:730–732

Odom DT, Dowell RD, Jacobsen ES, Nekludova L, Rolfe PA, Danford TW, Gifford DK, Fraenkel E, Bell GI, Young RA 2006Core transcriptional regulatory circuitry in human hepatocytes.Mol Syst Biol2:2006.0017

Rada-Iglesias A, Wallerman O, Koch C, Ameur A, Enroth S, Clelland G, Wester K, Wilcox S, Dovey OM, Ellis PD, Wraight VL, James K, Andrews R, Langford C, Dhami P, Carter N, Vetrie D, Ponten F, Komorowski J, Dunham I, Wadelius C 2005Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays.Hum Mol Genet14:3435–3447

Holloway MG, Laz EV, Waxman DJ 2006Codependence of growth hormone-responsive, sexually dimorphic hepatic gene expression on signal transducer and activator of transcription 5b and hepatic nuclear factor 4α.Mol Endocrinol20:647–660

Laz EV, Holloway MG, Chen CS, Waxman DJ 2007Characterization of three growth hormone-responsive transcription factors preferentially expressed in adult female liver.Endocrinology148:3327–3337

Wiwi CA, Gupte M, Waxman DJ 2004Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear factor 4α-deficient mice.Mol Endocrinol18:1975–1987

Nakayama K, Sudo Y, Sasaki Y, Iwata H, Takahashi M, Kamataki T 2001Studies on transcriptional regulation of Cyp3a16 gene in mouse livers by application of direct DNA injection method.Biochem Biophys Res Commun287:820–824

Sasaki Y, Takahashi Y, Nakayama K, Kamataki T 1999Cooperative regulation of CYP2C12 gene expression by STAT5 and liver-specific factors in female rats.J Biol Chem274:37117–37124

Strom A, Westin S, Eguchi H, Gustafsson JA, Mode A 1995Characterization of orphan nuclear receptor binding elements in sex-differentiated members of the CYP2C gene family expressed in rat liver.J Biol Chem270:11276–11281

Yokomori N, Nishio K, Aida K, Negishi M 1997Transcriptional regulation by HNF-4 of the steroid 15α-hydroxylase P450 (Cyp2a-4) gene in mouse liver.J Steroid Biochem Mol Biol62:307–314

Jaffe CA, Turgeon DK, Lown K, Demott-Friberg R, Watkins PB 2002 Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans. Am J Physiol Endocrinol Metab 283:E1008–E1015

Wolbold R, Klein K, Burk O, Nussler AK, Neuhaus P, Eichelbaum M, Schwab M, Zanger UM 2003Sex is a major determinant of CYP3A4 expression in human liver.Hepatology38:978–988

Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, Parviz F, Duncan SA, Inoue Y, Gonzalez FJ, Schuetz EG, Kim RB 2003The orphan nuclear receptor HNF4α determines PXR- and CAR-mediated xenobiotic induction of CYP3A4.Nat Med9:220–224

Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, Fackenthal JD, Rogan PK, Ring B, Wrighton SA, Schuetz EG 2003Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression.J Pharmacol Exp Ther307:906–922

Clodfelter KH, Holloway MG, Hodor P, Park SH, Ray WJ, Waxman DJ 2006Sex-dependent liver gene expression is extensive and largely dependent upon signal transducer and activator of transcription 5b (STAT5b): STAT5b-dependent activation of male genes and repression of female genes revealed by microarray analysis.Mol Endocrinol20:1333–1351

Holloway MG, Cui Y, Laz EV, Hosui A, Hennighausen L, Waxman DJ 2007Loss of sexually dimorphic liver gene expression upon hepatocyte-specific deletion of Stat5a-Stat5b locus.Endocrinology148:1977–1986

Waxman DJ, O’Connor C 2006Growth hormone regulation of sex-dependent liver gene expression.Mol Endocrinol20:2613–2629

Weng L, Dai H, Zhan Y, He Y, Stepaniants SB, Bassett DE 2006Rosetta error model for gene expression analysis.Bioinformatics22:1111–1121

Clodfelter KH, Miles GD, Wauthier V, Holloway MG, Zhang X, Hodor P, Ray WJ, Waxman DJ 2007Role of STAT5a in regulation of sex-specific gene expression in female but not male mouse liver revealed by microarray analysis.Physiol Genomics31:63–74

Yang X, Schadt EE, Wang S, Wang H, Arnold AP, Ingram-Drake L, Drake TA, Lusis AJ 2006Tissue-specific expression and regulation of sexually dimorphic genes in mice.Genome Res16:995–1004

Sjogren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Tornell J, Isaksson OG, Jansson JO, Ohlsson C 1999Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.Proc Natl Acad Sci USA96:7088–7092

Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW 1997Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression.Proc Natl Acad Sci USA94:7239–7244

Waxman DJ, Celenza JL 2003Sexual dimorphism of hepatic gene expression: novel biological role of KRAB zinc finger repressors revealed.Genes Dev17:2607–2613

Noshiro M, Serabjit-Singh CJ, Bend JR, Negishi M 1986Female-predominant expression of testosterone 16α-hydroxylase (“I”-P-450(16)α) and its repression in strain 129/J.Arch Biochem Biophys244:857–864

Tullis KM, Krebs CJ, Leung JY, Robins DM 2003The regulator of sex-limitation gene, Rsl, enforces male-specific liver gene expression by negative regulation.Endocrinology144:1854–1860

Krebs CJ, Larkins LK, Price R, Tullis KM, Miller RD, Robins DM 2003Regulator of sex-limitation (Rsl) encodes a pair of KRAB zinc-finger genes that control sexually dimorphic liver gene expression.Genes Dev17:2664–2674

Lahuna O, Rastegar M, Maiter D, Thissen JP, Lemaigre FP, Rousseau GG 2000Involvement of STAT5 (signal transducer and activator of transcription 5) and HNF-4 (hepatocyte nuclear factor 4) in the transcriptional control of the hnf6 gene by growth hormone.Mol Endocrinol14:285–294

Delesque-Touchard N, Park SH, Waxman DJ 2000Synergistic action of hepatocyte nuclear factors 3 and 6 on CYP2C12 gene expression and suppression by growth hormone-activated STAT5b. Proposed model for female specific expression of CYP2C12 in adult rat liver.J Biol Chem275:34173–34182

Lahuna O, Fernandez L, Karlsson H, Maiter D, Lemaigre FP, Rousseau GG, Gustafsson J, Mode A 1997Expression of hepatocyte nuclear factor 6 in rat liver is sex-dependent and regulated by growth hormone.Proc Natl Acad Sci USA94:12309–12313

Gardmo C, Mode A 2006In vivo transfection of rat liver discloses binding sites conveying GH-dependent and female-specific gene expression.J Mol Endocrinol37:433–441

Wang JC, Stafford JM, Granner DK 1998SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4.J Biol Chem273:30847–30850

Yoshida E, Aratani S, Itou H, Miyagishi M, Takiguchi M, Osumu T, Murakami K, Fukamizu A 1997Functional association between CBP and HNF4 in trans-activation.Biochem Biophys Res Commun241:664–669

Gyorffy B, Gyorffy A, Tulassay Z 2005[The problem of multiple testing and solutions for genome-wide studies].Orv Hetil146:559–563 (Hungarian)

Dennis G, Jr., Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA 2003 DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol 4:P3

Hosack DA, Dennis Jr G, Sherman BT, Lane HC, Lempicki RA 2003 Identifying biological themes within lists of genes with EASE. Genome Biol 4:R70

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G 2000Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.Nat Genet25:25–29