As the name suggests, hepatocyte nuclear factors are expressed predominantly in the liver. However HNFs are also expressed and play important roles in a number of other tissues so that the name hepatocyte nuclear factor is somewhat misleading. Nevertheless, the liver is the only tissue in which a significant number of different HNFs are expressed at the same time. In addition, there are a number of genes which contain multiple promoter and enhancer regions each regulated by a different HNF. Furthermore, efficient expression of these genes require synergistic activation by multiple HNFs. Hence hepatocyte nuclear factors function to ensure liver specific expression of certain genes.
As is the case with many transcription factors, HNFs regulate the expression of a wide variety of target genes and therefore functions. These functions (and especially functions involving the liver) include development and metabolichomeostasis of the organism. For example, HNFs influence expression of the insulin gene as well as genes involved in glucose transport and metabolism. In embryo development, HNF4α is thought to have an important role in the development of the liver, kidney, and intestines.
Disease implication
Variants of the genes can cause several relatively rare forms of MODY, an inherited, early onset form of diabetes. Mutations in the HNF4α, HNF1α, or HNF1β genes are linked to MODY 1, MODY 3, and MODY 5 respectively.[3] Mutations in HNF genes are also associated with a number of others diseases including hepatic adenomas and renal cysts.
Members
The following is a list of human hepatocyte nuclear factors (see also boxes to the right for additional information about these proteins):
HNF1
Members of the HNF1 subfamily contain a POU-homeodomain and bind to DNA as homodimers.
^Costa RH, Kalinichenko VV, Holterman AX, Wang X (2003). "Transcription factors in liver development, differentiation, and regeneration". Hepatology. 38 (6): 1331–47. doi:10.1016/j.hep.2003.09.034. PMID 14647040. S2CID 2646966.
^Mitchell SM, Frayling TM (2002). "The role of transcription factors in maturity-onset diabetes of the young". Mol Genet Metab. 77 (1–2): 35–43. doi:10.1016/S1096-7192(02)00150-6. PMID 12359128.
^Ryffel GU (2001). "Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences". J Mol Endocrinol. 27 (1): 11–29. doi:10.1677/jme.0.0270011. PMID 11463573.
Additional images
Hepatocyte nuclear factor 1A bound to DNA
Different rendering of HNF1a bound to DNA
External links
Hepatocyte+Nuclear+Factors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Transcription networks in the liver
transthyretin promoter, an example of a regulatory region containing HNF binding sites
HNF4 in genetics of diabetes
August 21, 2023
hepatocyte, nuclear, factors, hnfs, group, phylogenetically, unrelated, transcription, factors, that, regulate, transcription, diverse, group, genes, into, proteins, these, proteins, include, blood, clotting, factors, addition, enzymes, transporters, involved,. Hepatocyte nuclear factors HNFs are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins These proteins include blood clotting factors and in addition enzymes and transporters involved with glucose cholesterol and fatty acid transport and metabolism 1 2 Contents 1 Function 2 Disease implication 3 Members 3 1 HNF1 3 2 HNF3 3 3 HNF4 3 4 HNF6 4 See also 5 References 6 Additional images 7 External linksFunction EditAs the name suggests hepatocyte nuclear factors are expressed predominantly in the liver However HNFs are also expressed and play important roles in a number of other tissues so that the name hepatocyte nuclear factor is somewhat misleading Nevertheless the liver is the only tissue in which a significant number of different HNFs are expressed at the same time In addition there are a number of genes which contain multiple promoter and enhancer regions each regulated by a different HNF Furthermore efficient expression of these genes require synergistic activation by multiple HNFs Hence hepatocyte nuclear factors function to ensure liver specific expression of certain genes As is the case with many transcription factors HNFs regulate the expression of a wide variety of target genes and therefore functions These functions and especially functions involving the liver include development and metabolic homeostasis of the organism For example HNFs influence expression of the insulin gene as well as genes involved in glucose transport and metabolism In embryo development HNF4a is thought to have an important role in the development of the liver kidney and intestines Disease implication EditVariants of the genes can cause several relatively rare forms of MODY an inherited early onset form of diabetes Mutations in the HNF4a HNF1a or HNF1b genes are linked to MODY 1 MODY 3 and MODY 5 respectively 3 Mutations in HNF genes are also associated with a number of others diseases including hepatic adenomas and renal cysts Members EditThe following is a list of human hepatocyte nuclear factors see also boxes to the right for additional information about these proteins HNF1 Edit Members of the HNF1 subfamily contain a POU homeodomain and bind to DNA as homodimers HNF1a TCF1 MODY3 related disease MODY 3 HNF1b TCF2 MODY5 related disease MODY 5 hepatocyte nuclear factor 1 alpha Structure of the hepatocyte nuclear factor 1A green cartoon bound to DNA magenta based on the crystallographic coordinates PDB 1IC8 IdentifiersSymbolHNF1AAlt symbolsMODY3 HNF1 LFB1 TCF1NCBI gene6927HGNC11621OMIM142410PDB1JB6RefSeqNM 000545UniProtP20823Other dataLocusChr 12 q24 3 12q24 3Search forStructuresSwiss modelDomainsInterPro hepatocyte nuclear factor 1 betaIdentifiersSymbolTCF2Alt symbolsHNF1beta LFB3 MODY5 VHNF1NCBI gene6928HGNC11630OMIM189907PDB2H8RRefSeqNM 000458UniProtP35680Other dataLocusChr 17 q12 17q12Search forStructuresSwiss modelDomainsInterProHNF3 Edit The HNF3 subfamily members contain a winged helix DNA binding domain and bind to DNA as monomers HNF3a FOXA1 forkhead box A1 HNF3b FOXA2 forkhead box A2 HNF3g FOXA3 forkhead box A3 hepatocyte nuclear factor 3 alphaIdentifiersSymbolFOXA1Alt symbolsHNF3ANCBI gene3169HGNC5021OMIM602294RefSeqNM 004496UniProtP55317Other dataLocusChr 14 q12 q13Search forStructuresSwiss modelDomainsInterPro hepatocyte nuclear factor 3 betaIdentifiersSymbolFOXA2Alt symbolsHNF3BNCBI gene3170HGNC5022OMIM600288RefSeqNM 021784UniProtQ9Y261Other dataLocusChr 20 p1120p11Search forStructuresSwiss modelDomainsInterPro hepatocyte nuclear factor 3 gammaIdentifiersSymbolFOXA3Alt symbolsHNF3GNCBI gene3171HGNC5023OMIM602295RefSeqNM 004497UniProtP55318Other dataLocusChr 19 q13 2 q13 4Search forStructuresSwiss modelDomainsInterProHNF4 Edit Members of the HNF4 subfamily are nuclear receptors and bind to DNA either as homodimers or RXR heterodimers HNF4a TCF14 MODY1 HNF4ghepatocyte nuclear factor 4alphaIdentifiersSymbolHNF4AAlt symbolsMODY MODY1 NR2A1 TCF14NCBI gene3172HGNC5024OMIM600281PDB1M7WRefSeqNM 001030004UniProtP41235Other dataLocusChr 20 q12 20q13 1Search forStructuresSwiss modelDomainsInterPro hepatocyte nuclear factor 4gammaIdentifiersSymbolHNF4GAlt symbolsNR2A2NCBI gene3174HGNC5026OMIM605966PDB1LV2RefSeqNM 004133UniProtQ14541Other dataLocusChr 8 q21 q22Search forStructuresSwiss modelDomainsInterProHNF6 Edit The HNF6 subfamily members contain a cut homeodomain ONECUT bind to DNA as monomers HNF6a OC 1 ONECUT1 ONECUT1 HNF6b OC 2 ONECUT2 ONECUT2 hepatocyte nuclear factor 6 alphaIdentifiersSymbolONECUT1Alt symbolsHNF6 HNF6ANCBI gene3175HGNC8138OMIM604164RefSeqNM 004498UniProtQ9UBC0Other dataLocusChr 15 q21 q21 2Search forStructuresSwiss modelDomainsInterPro hepatocyte nuclear factor 6 betaIdentifiersSymbolONECUT2Alt symbolsHNF6B OC 2NCBI gene9480HGNC8139OMIM604894RefSeqNM 004852UniProtO95948Other dataLocusChr 18 q21 1 21 2Search forStructuresSwiss modelDomainsInterProSee also EditHNF4 Transcription genetics Maturity onset diabetes of the youngReferences Edit Costa RH Kalinichenko VV Holterman AX Wang X 2003 Transcription factors in liver development differentiation and regeneration Hepatology 38 6 1331 47 doi 10 1016 j hep 2003 09 034 PMID 14647040 S2CID 2646966 Mitchell SM Frayling TM 2002 The role of transcription factors in maturity onset diabetes of the young Mol Genet Metab 77 1 2 35 43 doi 10 1016 S1096 7192 02 00150 6 PMID 12359128 Ryffel GU 2001 Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor HNF 1 and HNF4 families functional and pathological consequences J Mol Endocrinol 27 1 11 29 doi 10 1677 jme 0 0270011 PMID 11463573 Additional images Edit Hepatocyte nuclear factor 1A bound to DNA 1 Different rendering of HNF1a bound to DNAExternal links EditHepatocyte Nuclear Factors at the U S National Library of Medicine Medical Subject Headings MeSH Transcription networks in the liver transthyretin promoter an example of a regulatory region containing HNF binding sites HNF4 in genetics of diabetes Retrieved from https en wikipedia org w index php title Hepatocyte nuclear factors amp oldid 1136190526, wikipedia, wiki, book, books, library,
