Hepatocyte nuclear factors
Encyclopedia
Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription
of a diverse group of genes
into protein
s. These proteins include blood clotting factors and in addition, enzyme
s and transporter
s involved with glucose
, cholesterol
, and fatty acid
transport and metabolism
.
. 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.
, an inherited, early onset form of diabetes. Mutations in the HNF4α, HNF1α, or HNF1β genes are linked to MODY1, MODY3, and MODY5 respectively. Mutations in HNF genes are also associated with a number of others diseases including hepatic adenomas and renal cysts.
and bind to DNA as monomers.
s and bind to DNA either as homodimers or RXR
heterodimers.
) bind to DNA as monomers.
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of a diverse group of genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
into protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. These proteins include blood clotting factors and in addition, enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s and transporter
Solute carrier family
The solute carrier group of membrane transport proteins include over 300 members organized into 51 families. The SLC gene nomenclature system was originally proposed by the Human Genome Organization and is the basis for the official HUGO names of the genes that encode these transporters...
s involved with glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, and fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
transport and metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
.
Function
As the name suggests, hepatocyte nuclear factors are expressed predominately in the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. 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
Enhancer (genetics)
In genetics, an enhancer is a short region of DNA that can be bound with proteins to enhance transcription levels of genes in a gene cluster...
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
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
and metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
homeostasis of the organism. For example, HNFs influence expression of the insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
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
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, and intestines.
Disease implication
Variants of the genes can cause several relatively rare forms of MODYMody
Mody may refer to:* Maturity onset diabetes of the young * Hormusjee Naorojee Mody...
, an inherited, early onset form of diabetes. Mutations in the HNF4α, HNF1α, or HNF1β genes are linked to MODY1, MODY3, and MODY5 respectively. 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.- HNF1αHNF1AHNF1 homeobox A , also known as HNF1A, is a human gene.The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes.-Interactions:HNF1A has been shown to interact with PCAF, Src,...
/TCF1/MODY3 - HNF1βHNF1BHNF1 homeobox B , also known as HNF1B or transcription factor 2 , is a human gene.-Further reading:...
/TCF2/MODY5
HNF3
The HNF3 subfamily members contain a winged helix DNA-binding domainWinged-helix transcription factors
Consisting of about 110 amino acids, the domain in winged-helix transcription factors has four helices and a two-strand beta-sheet.These proteins are classified into 17 families called FoxA-FoxQ....
and bind to DNA as monomers.
- HNF3α/FOXA1FOXA1Forkhead box protein A1 , also known as hepatocyte nuclear factor 3-alpha , is a protein that in humans is encoded by the FOXA1 gene.- Function :FOXA1 is a member of the forkhead class of DNA-binding proteins...
(forkhead boxFOX proteinsFOX proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity...
A1) - HNF3β/FOXA2FOXA2Hepatocyte nuclear factor 3-beta , also known as forkhead box protein A2 or transcription factor 3B is a protein that in humans is encoded by the FOXA2 gene.- Function :...
(forkhead box A2) - HNF3γ/FOXA3FOXA3Hepatocyte nuclear factor 3-gamma , also known as forkhead box protein A3 or transcription factor 3G is a protein that in humans is encoded by the FOXA3 gene.- Function :...
(forkhead box A3)
HNF4
Members of the HNF4 subfamily are nuclear receptorNuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
s and bind to DNA either as homodimers or RXR
RXR
RXR may stand for*The Retinoid X receptor found in cells.*A Railway Crossing also called a Level crossing*Revco, American company, NYSE code RXR...
heterodimers.
- HNF4αHepatocyte nuclear factor 4 alphaHepatocyte nuclear factor 4 alpha also known as NR2A1 is a nuclear receptor that in humans is encoded by the HNF4A gene.- Function :...
/TCF14/MODY1 - HNF4γHepatocyte nuclear factor 4 gammaHepatocyte nuclear factor 4 gamma also known as NR2A2 is a nuclear receptor that in humans is encoded by the HNF4G gene....
HNF6
The HNF6 subfamily members contain a cut-homeodomain (ONECUTCUT domain
In molecular biology, the CUT domain is a DNA-binding motif which can bind independently or in cooperation with the homeodomain, which is often found downstream of the CUT domain...
) bind to DNA as monomers.
- HNF6α/OC-1/ONECUT1
- HNF6β/OC-2/ONECUT2
See also
- HNF4
- Transcription (genetics)Transcription (genetics)Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
- Maturity onset diabetes of the youngMaturity onset diabetes of the youngMaturity onset diabetes of the young refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene disrupting insulin production...
External links