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 HNF4β 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
hepatocyte nuclear factor 1, alpha
Identifiers
Symbol
TCF1
Alt. Symbols
MODY3,HNF1, LFB1, HNF1A
Entrez
6927
HUGO
11621
OMIM
142410
PDB
1JB6
RefSeq
NM_000545
UniProt
P20823
Other data
Locus
Chr. 12 q24.3-12q24.3
hepatocyte nuclear factor 1, beta
Identifiers
Symbol
TCF2
Alt. Symbols
MODY5,LFB3, VHNF1, HNF1beta
Entrez
6928
HUGO
11630
OMIM
189907
PDB
2H8R
RefSeq
NM_000458
UniProt
P35680
Other data
Locus
Chr. 17 q12-17q12
hepatocyte nuclear factor 3, alpha
Identifiers
Symbol
FOXA1
Alt. Symbols
HNF3A
Entrez
3169
HUGO
5021
OMIM
602294
PDB
1KQ8
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
hepatocyte nuclear factor 4, alpha
Identifiers
Symbol
HNF4A
Alt. Symbols
TCF14, MODY, MODY1
Entrez
3172
HUGO
5024
OMIM
600281
PDB
1M7W
RefSeq
NM_001030004
UniProt
P41235
Other data
Locus
Chr. 20 q12-20q13.1
hepatocyte nuclear factor 4, gamma
Identifiers
Symbol
HNF4G
Entrez
3174
HUGO
5026
OMIM
605966
PDB
1LV2
RefSeq
NM_004133
UniProt
Q14541
Other data
Locus
Chr. 8 q21-q22
hepatocyte nuclear factor 6, alpha
Identifiers
Symbol
ONECUT1
Alt. Symbols
HNF6, HNF6A
Entrez
3175
HUGO
8138
OMIM
604164
PDB
1S7E
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
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.
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
^ Costa RH, Kalinichenko VV, Holterman AX, Wang X (2003). "Transcription factors in liver development, differentiation, and regeneration". Hepatology38 (6): 1331-47. doi:10.1016/j.hep.2003.09.034. PMID 14647040.
^ Mitchell SM, Frayling TM (2002). "The role of transcription factors in maturity-onset diabetes of the young". Mol Genet Metab77 (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 Endocrinol27 (1): 11-29. doi:10.1677/jme.0.0270011. PMID 11463573.