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
SymbolTCF1
Alt. symbolsMODY3, HNF1, LFB1, HNF1A
Entrez6927
HUGO11621
OMIM142410
PDB1JB6
RefSeqNM_000545
UniProtP20823
Other data
LocusChr. 12 q24.3-12q24.3
hepatocyte nuclear factor 1, beta
Identifiers
SymbolTCF2
Alt. symbolsHNF1beta, LFB3 MODY5, VHNF1
Entrez6928
HUGO11630
OMIM189907
PDB2H8R
RefSeqNM_000458
UniProtP35680
Other data
LocusChr. 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
SymbolFOXA1
Alt. symbolsHNF3A
Entrez3169
HUGO5021
OMIM602294
RefSeqNM_004496
UniProtP55317
Other data
LocusChr. 14 q12-q13
hepatocyte nuclear factor 3,
beta
Identifiers
SymbolFOXA2
Alt. symbolsHNF3B
Entrez3170
HUGO5022
OMIM600288
RefSeqNM_021784
UniProtQ9Y261
Other data
LocusChr. 20 p1120p11
hepatocyte nuclear factor 3,
gamma
Identifiers
SymbolFOXA3
Alt. symbolsHNF3G
Entrez3171
HUGO5023
OMIM602295
RefSeqNM_004497
UniProtP55318
Other data
LocusChr. 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
SymbolHNF4A
Alt. symbolsMODY, MODY1, NR2A1, TCF14
Entrez3172
HUGO5024
OMIM600281
PDB1M7W
RefSeqNM_001030004
UniProtP41235
Other data
LocusChr. 20 q12-20q13.1
hepatocyte nuclear factor 4
gamma
Identifiers
SymbolHNF4G
Alt. symbolsNR2A2
Entrez3174
HUGO5026
OMIM605966
PDB1LV2
RefSeqNM_004133
UniProtQ14541
Other data
LocusChr. 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
SymbolONECUT1
Alt. symbolsHNF6, HNF6A
Entrez3175
HUGO8138
OMIM604164
RefSeqNM_004498
UniProtQ9UBC0
Other data
LocusChr. 15 q21-q21.2
hepatocyte nuclear factor 6, beta
Identifiers
SymbolONECUT2
Alt. symbolsHNF6B, OC-2
Entrez9480
HUGO8139
OMIM604894
RefSeqNM_004852
UniProtO95948
Other data
LocusChr. 18 q21.1-21.2

See also[edit]

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]

External links[edit]