Hepatocyte nuclear factors

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

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

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

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.

• HNF1α/TCF1/MODY3 (TCF1)
• HNF1β/TCF2/MODY5 (TCF2)

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. 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

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

• HNF3α/FOXA1 (forkhead box A1)
• HNF3β/FOXA2 (forkhead box A2)
• HNF3γ/FOXA3 (forkhead box A3)

HNF4

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

• HNF4α/TCF14/MODY1 (HNF4a)
• HNF4γ (HNF4g)

HNF6

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

• HNF6α/OC-1/ONECUT1 (ONECUT1)
• HNF6β/OC-2/ONECUT2 (ONECUT2)

References

Additional images

• 

  Hepatocyte nuclear factor 1A bound to DNA [1]

• 

  Different rendering of HNF1a bound to DNA

See also

• HNF4
• Transcription (genetics)
• Maturity onset diabetes of the young

External links

• Hepatocyte Nuclear Factors at the US 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