My watch list

Home
Encyclopedia
Hepatocyte_nuclear_factors

Hepatocyte nuclear factors

Hepatocyte nuclear factors (HNFs) are a subfamily of 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]

Additional recommended knowledge

Daily Sensitivity Test

What is the Sensitivity of my Balance?

Daily Visual Balance Check

1 Function
2 Disease implication
3 Members
- 3.1 HNF1
- 3.2 HNF3
- 3.3 HNF4
- 3.4 HNF6
4 References
5 See also

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 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.

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

HNF3

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

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

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

^ 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.
^ 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.
^ 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.

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH)	ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1
(1.3) bHLH-ZIP	Myc • MITF • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH)	AP-2

(2) Zinc finger
DNA-binding domains

(2.1) Nuclear receptor (Cys₄)	subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys₄	GATA (1, 2, 3, 4, 5, 6)
(2.3) Cys₂His₂	General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys₆	HIVEP1

(3) Helix-turn-helix
domains

(3.1) Homeo domain	ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7)
(3.2) Paired box	PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
(3.3) Fork head / winged helix	E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3)
(3.4) Heat Shock Factors	HSF1
(3.5) Tryptophan clusters	ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB
(3.6) TEA domain	transcriptional enhancer factor 1, 2

(4) β-Scaffold factors with
minor groove contacts

(4.1) Rel homology region	NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4)
(4.2) STAT	STAT (1, 2, 3, 4, 5, 6)
(4.3) p53	p53
(4.4) MADS box	Mef2 (A, B, C, D) • SRF
(4.7) High mobility group	HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1
(4.10) Cold-shock domain	CSDA
(4.11) Runt	CBF (RUNX1, RUNX2, RUNX3)

(0) Other
transcription factors

(0.2) HMGI(Y)	HMGA (1, 2)
(0.3) Pocket domain	Rb • RBL1 • RBL2
(0.6) Miscellaneous	ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD

Categories: Metabolism | Signal transduction | Transcription factors

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Hepatocyte_nuclear_factors". A list of authors is available in Wikipedia.

Last viewed

How do good metals go bad? - New measurements have solved a mystery in solid state physics: How is it that certain metals do not seem to adhere to the valid rules?