Hepatocyte nuclear factors

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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]

Function[edit]

As the name suggests, hepatocyte nuclear factors are expressed predominately 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, HNF4α is thought to have an important role in the development of the liver, kidney, and intestines.

Disease implication[edit]

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 MODY1, MODY3, and MODY5 respectively.[3] Mutations in HNF genes are also associated with a number of others diseases including hepatic adenomas and renal cysts.

Members[edit]

The 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.

hepatocyte nuclear factor 1, alpha
1IC8.png
Structure of the hepatocyte nuclear factor 1A (green cartoon) bound to DNA (magenta) based on the crystallographic coordinates PDB 1IC8.
Identifiers
Symbol TCF1
Alt. symbols MODY3,HNF1, LFB1, HNF1A
Entrez 6927
HUGO 11621
OMIM 142410
PDB 1JB6 (RCSB PDB PDBe PDBj)
RefSeq NM_000545
UniProt P20823
Other data
Locus Chr. 12 q24.3-12q24.3
hepatocyte nuclear factor 1, beta
Identifiers
Symbol TCF2
Alt. symbols HNF1beta, LFB3 MODY5, VHNF1
Entrez 6928
HUGO 11630
OMIM 189907
PDB 2H8R (RCSB PDB PDBe PDBj)
RefSeq NM_000458
UniProt P35680
Other data
Locus Chr. 17 q12-17q12

HNF3[edit]

The HNF3 subfamily members contain a winged helix DNA-binding domain and bind to DNA as monomers.

hepatocyte nuclear factor 3,
alpha
Identifiers
Symbol FOXA1
Alt. symbols HNF3A
Entrez 3169
HUGO 5021
OMIM 602294
RefSeq NM_004496
UniProt P55317
Other data
Locus Chr. 14 q12-q13
hepatocyte nuclear factor 3,
beta
Identifiers
Symbol FOXA2
Alt. symbols HNF3B
Entrez 3170
HUGO 5022
OMIM 600288
RefSeq NM_021784
UniProt Q9Y261
Other data
Locus Chr. 20 p1120p11
hepatocyte nuclear factor 3,
gamma
Identifiers
Symbol FOXA3
Alt. symbols HNF3G
Entrez 3171
HUGO 5023
OMIM 602295
RefSeq NM_004497
UniProt P55318
Other data
Locus Chr. 19 q13.2-q13.4

HNF4[edit]

Members of the HNF4 subfamily are nuclear receptors and bind to DNA either as homodimers or RXR heterodimers.

hepatocyte nuclear factor 4
alpha
Identifiers
Symbol HNF4A
Alt. symbols MODY, MODY1, NR2A1, TCF14
Entrez 3172
HUGO 5024
OMIM 600281
PDB 1M7W (RCSB PDB PDBe PDBj)
RefSeq NM_001030004
UniProt P41235
Other data
Locus Chr. 20 q12-20q13.1
hepatocyte nuclear factor 4
gamma
Identifiers
Symbol HNF4G
Alt. symbols NR2A2
Entrez 3174
HUGO 5026
OMIM 605966
PDB 1LV2 (RCSB PDB PDBe PDBj)
RefSeq NM_004133
UniProt Q14541
Other data
Locus Chr. 8 q21-q22

HNF6[edit]

The HNF6 subfamily members contain a cut-homeodomain (ONECUT) bind to DNA as monomers.

hepatocyte nuclear factor 6, alpha
Identifiers
Symbol ONECUT1
Alt. symbols HNF6, HNF6A
Entrez 3175
HUGO 8138
OMIM 604164
RefSeq NM_004498
UniProt Q9UBC0
Other data
Locus Chr. 15 q21-q21.2
hepatocyte nuclear factor 6, beta
Identifiers
Symbol ONECUT2
Alt. symbols HNF6B, OC-2
Entrez 9480
HUGO 8139
OMIM 604894
RefSeq NM_004852
UniProt O95948
Other data
Locus Chr. 18 q21.1-21.2

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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]

See also[edit]

External links[edit]