AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene. [5]
AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene. [5]
ARID2 is a subunit of the PBAF chromatin-remodeling complex, which facilitates ligand-dependent transcriptional activation by nuclear receptors. [5]
The ARID2 protein contains two conserved C-terminal C2H2 zinc fingers motifs, a region rich in the amino acid residues proline and glutamine, a RFX (regulatory factor X)-type winged-helix DNA-binding domain, and a conserved N-terminal A T-rich DNA interaction domain—the last domain for which the protein is named. [6]
Mutation studies have revealed ARID2 to be a significant tumor suppressor in many cancer subtypes. ARID2 mutations are prevalent in hepatocellular carcinoma [7] and melanoma. [8] [9] Mutations are present in a smaller but significant fraction in a wide range of other tumors. [10] ARID2 mutations are enriched in hepatitis C virus-associated hepatocellular carcinoma in the US and European patient populations compared with the overall mutation frequency. [6]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Eye Histopathology | Normal |
| Salmonella infection | Normal [11] |
| Citrobacter infection | Normal [12] |
| All tests and analysis from [13] [14] |
The ARID2 gene, located on chromosome 12q in humans, consists of 21 exons; orthologs are known from mouse, rat, cattle, chicken, and mosquito. [6] Model organisms have been used in the study of ARID2 function. A conditional knockout mouse line, called Arid2tm1a(EUCOMM)Wtsi [15] [16] was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. [17] [18] [19]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [13] [20] Twenty six tests were carried out on mutant adult mice and two significant abnormalities were observed. [13] A recessive lethal study found fewer homozygous mutant embryos during gestation than predicted by Mendelian ratio. In a second study, no homozygous mutant animals survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; these displayed no abnormalities. [13]
In molecular biology, SWI/SNF, is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is packaged. This complex is composed of several proteins – products of the SWI and SNF genes, as well as other polypeptides. It possesses a DNA-stimulated ATPase activity that can destabilize histone-DNA interactions in reconstituted nucleosomes in an ATP-dependent manner, though the exact nature of this structural change is unknown. The SWI/SNF subfamily provides crucial nucleosome rearrangement, which is seen as ejection and/or sliding. The movement of nucleosomes provides easier access to the chromatin, allowing genes to be activated or repressed.
Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.
Transcription activator BRG1 also known as ATP-dependent chromatin remodeler SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.
Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene.
Probable global transcription activator SNF2L2 is a protein that in humans is encoded by the SMARCA2 gene.
Actin-like protein 6A is a protein that in humans is encoded by the ACTL6A gene.
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.
AT-rich interactive domain-containing protein 1B is a protein that in humans is encoded by the ARID1B gene. ARID1B is a component of the human SWI/SNF chromatin remodeling complex.
DNA repair and recombination protein RAD54-like is a protein that in humans is encoded by the RAD54L gene.
Tyrosine-protein kinase, or Bromodomain adjacent to zinc finger domain, 1B (BAZ1B) is an enzyme that in humans is encoded by the BAZ1B gene.
Ubiquitin-associated protein 1 is a protein that in humans is encoded by the UBAP1 gene.
Protein polybromo-1 (PB1) also known as BRG1-associated factor 180 (BAF180) is a protein that in humans is encoded by the PBRM1 gene.
Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 is a protein that in humans is encoded by the SMARCD3 gene.
Lymphoid-specific helicase (Lsh) is a member of the SNF2 helicase family of chromatin remodeling proteins that in humans is encoded by the HELLS gene.
Probable global transcription activator SNF2L1 is a protein that in humans is encoded by the SMARCA1 gene.
Vacuolar-sorting protein SNF8 is a protein that in humans is encoded by the SNF8 gene.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 is a protein that in humans is encoded by the SMARCAL1 gene.
SET and MYND domain-containing protein 4 is a protein that in humans is encoded by the SMYD4 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.