Hepatocyte nuclear factors

protein
Name= hepatocyte nuclear factor 1, alpha
caption=Structure of the hepatocyte nuclear factor 1A (green cartoon) bound to DNA (magenta) based on the crystallographic coordinates PDB|1IC8.

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width=
HGNCid= 11621
Symbol= TCF1
AltSymbols= MODY3,HNF1, LFB1, HNF1A
EntrezGene= 6927
OMIM= 142410
RefSeq= NM_000545
UniProt= P20823
PDB= 1JB6
ECnumber=
Chromosome=12
Arm=q
Band=24.3
LocusSupplementaryData=-12q24.3protein
Name= hepatocyte nuclear factor 1, beta
caption=


width=
HGNCid= 11630
Symbol= TCF2
AltSymbols= MODY5,LFB3, VHNF1, HNF1beta
EntrezGene= 6928
OMIM= 189907
RefSeq= NM_000458
UniProt= P35680
PDB= 2H8R
ECnumber=
Chromosome=17
Arm=q
Band=12
LocusSupplementaryData=-17q12protein
Name=hepatocyte nuclear factor 3, alpha
caption=


width=
HGNCid= 5021
Symbol= FOXA1
AltSymbols= HNF3A
EntrezGene= 3169
OMIM= 602294
RefSeq= NM_004496
UniProt= P55317
PDB= 1KQ8
ECnumber=
Chromosome=14
Arm=q
Band=12
LocusSupplementaryData=-q13protein
Name=hepatocyte nuclear factor 3, beta
caption=


width=
HGNCid= 5022
Symbol= FOXA2
AltSymbols= HNF3B
EntrezGene= 3170
OMIM= 600288
RefSeq= NM_021784
UniProt= Q9Y261
PDB=
ECnumber=
Chromosome=20
Arm=p
Band=11
LocusSupplementaryData=20p11protein
Name=hepatocyte nuclear factor 3, gamma
caption=


width=
HGNCid= 5023
Symbol= FOXA3
AltSymbols= HNF3G
EntrezGene= 3171
OMIM= 602295
RefSeq= NM_004497
UniProt= P55318
PDB=
ECnumber=
Chromosome=19
Arm=q
Band=13.2
LocusSupplementaryData=-q13.4protein
Name=hepatocyte nuclear factor 4 alpha
caption=


width=
HGNCid=5024
Symbol=HNF4A
AltSymbols=TCF14, MODY, MODY1
EntrezGene=3172
OMIM=600281
RefSeq=NM_001030004
UniProt=P41235
PDB=1M7W
ECnumber=
Chromosome=20
Arm=q
Band=12
LocusSupplementaryData=-20q13.1protein
Name=hepatocyte nuclear factor 4 gamma
caption=


width=
HGNCid=5026
Symbol=HNF4G
AltSymbols=
EntrezGene=3174
OMIM=605966
RefSeq=NM_004133
UniProt=Q14541
PDB=1LV2
ECnumber=
Chromosome=8
Arm=q
Band=21
LocusSupplementaryData=-q22protein
Name=hepatocyte nuclear factor 6, alpha
caption=


width=
HGNCid= 8138
Symbol= ONECUT1
AltSymbols=HNF6, HNF6A
EntrezGene= 3175
OMIM= 604164
RefSeq= NM_004498
UniProt= Q9UBC0
PDB=1S7E
ECnumber=
Chromosome=15
Arm=q
Band=21
LocusSupplementaryData=-q21.2protein
Name=hepatocyte nuclear factor 6, beta
caption=


width=
HGNCid= 8139
Symbol= ONECUT2
AltSymbols=HNF6B, OC-2
EntrezGene= 9480
OMIM= 604894
RefSeq= NM_004852
UniProt= O95948
PDB=
ECnumber=
Chromosome=18
Arm=q
Band=21.1
LocusSupplementaryData=-21.2

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.cite journal |author=Costa RH, Kalinichenko VV, Holterman AX, Wang X |title=Transcription factors in liver development, differentiation, and regeneration |journal= Hepatology |volume=38 |issue=6 |pages=1331–47 |year=2003| doi= 10.1016/j.hep.2003.09.034 |pmid= 14647040] cite journal |author=Mitchell SM, Frayling TM |title=The role of transcription factors in maturity-onset diabetes of the young |journal= Mol Genet Metab |volume=77 |issue=1-2 |pages=35–43 |year=2002| doi= 10.1016/S1096-7192(02)00150-6 |pmid= 12359128]

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 HNF4β genes are linked to , , and respectively.cite journal |author=Ryffel GU |title=Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences |journal= J Mol Endocrinol |volume=27 |issue=1 |pages=11–29 |year=2001| doi= 10.1677/jme.0.0270011 |pmid= 11463573] 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/ (Gene|TCF1)
* HNF1β/TCF2/ (Gene|TCF2)

HNF3

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

* HNF3α/FOXA1 (forkhead box A1) (Gene|FOXA1)
* HNF3β/FOXA2 (forkhead box A2) (Gene|FOXA2)
* HNF3γ/FOXA3 (forkhead box A3) (Gene|FOXA3)

= HNF4 =

Members of the HNF4 subfamily are nuclear receptors and bind to DNA either as homodimers or RXR heterodimers.
* HNF4α/TCF14/ (Gene|HNF4a)
* HNF4γ (Gene|HNF4g)

HNF6

The HNF6 subfamily members contain a cut-homeodomain (ONECUT) bind to DNA as monomers.
* HNF6α/OC-1/ONECUT1 (Gene|ONECUT1)
* HNF6β/OC-2/ONECUT2 (Gene|ONECUT2)

References

Additional images

ee also

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

External links

*
* [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=eurekah.section.67442 Transcription networks in the liver]
* [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.figgrp.2646 transthyretin promoter, an example of a regulatory region containing HNF binding sites]
* [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=diabetes.section.653 HNF4 in genetics of diabetes]