AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

which in humans is encoded by the ''ARID4A''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

The protein encoded by this gene is a ubiquitously expressed

nuclear Nuclear may refer to: Physics Relating to the nucleus of the atom: *Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics *Nuclear space *Nuclear ...

protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit

HDAC Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...

s and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described.

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used in the study of ARID4A function. A conditional

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

line, called ''Arid4a^{tm1a(EUCOMM)Wtsi}'' was generated as part of the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to cr ...

program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the

Wellcome Trust Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is located on the Wellcome G ...

. Male and female animals underwent a standardized

phenotypic screen In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...

to determine the effects of deletion. Twenty five tests were carried out and nine

phenotypes In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...

were reported. Fewer

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

embryos were identified during gestation than expected, and in a separate study less than the predicted

Mendelian ratio Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later popularized ...

survived until

weaning Weaning is the process of gradually introducing an infant human or another mammal to what will be its adult diet while withdrawing the supply of its mother's milk. The process takes place only in mammals, as only mammals produce milk. The infan ...

. Homozygous mutant male adults has a reduced body weight curve and a decreased grip strength. Homozygous mutant adults of both sexes had a decreased body weight as determined by

DEXA Dual-energy X-ray absorptiometry (DXA, or DEXA) is a means of measuring bone mineral density (BMD) using spectral imaging. Two X-ray beams, with different energy levels, are aimed at the patient's bones. When soft tissue absorption is subtracted ...

, displayed

vertebral fusion Spinal fusion, also called spondylodesis or spondylosyndesis, is a neurosurgical or orthopedic surgical technique that joins two or more vertebrae. This procedure can be performed at any level in the spine (cervical, thoracic, or lumbar) and pre ...

and had clinical chemistry abnormalities including

hypoalbuminemia Hypoalbuminemia (or hypoalbuminaemia) is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or ...

and decreased circulating

fructosamine Fructosamines are compounds that result from glycation reactions between a sugar (such as fructose or glucose) and a primary amine, followed by isomerization via the Amadori rearrangement. Biologically, fructosamines are recognized by fructosamine ...

levels. They also had haematological defects and an increased

NK cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

number.

Interactions

ARID4A has been shown to

interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...

with Retinoblastoma protein.

References

External links

* * * {{Transcription factors, g0 Transcription factors Genes mutated in mice

Function

Model organisms

Interactions

References

Further reading

External links