Protein Jumonji 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, respo ...
that in humans is encoded by the ''JARID2''
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 ba ...
.
JARID2 is a member of the
alpha-ketoglutarate-dependent hydroxylase superfamily.
Jarid2 (jumonji, AT rich interactive domain 2) is a protein coding gene that functions as a putative
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
. Distinguished as a
nuclear protein A nuclear protein is a protein found in the cell nucleus. Proteins are transported inside the nucleus with the help of the nuclear pore complex, which acts a barrier between cytoplasm and nuclear membrane. The import and export of proteins through ...
necessary for mouse
embryogenesis
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
, Jarid2 is a member of the jumonji family that contains a DNA binding domain known as the
AT-rich interaction domain (ARID).
''In vitro'' studies of Jarid2 reveal that ARID along with other functional domains are involved in DNA binding, nuclear localization,
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
al repression,
and recruitment of Polycomb-repressive complex 2 (PRC2).
Intracellular mechanisms underlying these interactions remain largely unknown.
In search of developmentally important genes, Jarid2 has previously been identified by
gene trap Gene trapping is a High-throughput screening, high-throughput approach that is used to introduce insertional mutations across an organism's genome.
Method
Trapping is performed with gene trap vectors whose principal element is a gene trapping cas ...
technology as an important factor necessary for
organ development.
During mouse organogenesis, Jarid2 is involved in the formation of the
neural tube and development of the liver, spleen, thymus and cardiovascular system.
Continuous Jarid2 expression in the tissues of the heart, highlight its presiding role in the development of both the embryonic and the adult heart.
Mutant models of Jarid2 embryos show severe heart malformations, ventricular septal defects,
noncompaction of the ventricular wall, and
atrial enlargement
Atrial enlargement refers to a condition where the left atrium or right atrium of the heart is larger than would be expected. It can also affect both atria.
Types include:
* Left atrial enlargement
* Right atrial enlargement
References
Ca ...
.
Homozygous mutants of Jarid2 are found to die soon after birth.
Overexpression of the mouse Jarid2 gene has been reported to repress
cardiomyocyte proliferation Cardiomyocyte proliferation refers to the ability of cardiac muscle cells to progress through the cell cycle and continue to divide. Traditionally, cardiomyocytes were believed to have little to no ability to proliferate and regenerate after birth. ...
through it close interaction with retinoblastoma protein (Rb), a master cell cycle regulator.
Retinoblastoma-binding protein-2 and the human SMCX protein share regions of homology between mice and humans.
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 JARID2 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 ''Jarid2
tm1a(KOMP)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 crea ...
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 proper ...
to determine the effects of deletion.
Twenty six tests were carried out and two
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 proper ...
were reported.
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 but almost half showed signs of
oedema
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
, and in a separate study, only 1% survived until
weaning (significantly less than the
Mendelian ratio). The remaining tests were carried out on
heterozygous
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 adult mice; no significant abnormalities were observed in these animals.
References
Further reading
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External links
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{{Portal bar, Biology, border=no
Human 2OG oxygenases
EC 1.14.11
Transcription factors
Genes mutated in mice