AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene. [5] [6] [7]
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene. [5] [6] [7]
ARID1A is a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has an ARID domain, which is a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SWI/SNF complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. The protein encoded by this gene confers specificity to the SWI/SNF complex and recruits the complex to its targets through either protein-DNA or protein-protein interactions. [8] Two transcript variants encoding different isoforms have been found for this gene. [7]
Gene encoding for ARID1A is the most frequently mutated SWI/SNF subunit across cancers. [9] This gene has been commonly found mutated in different cancers leading to loss of function, including gastric cancers, [10] colon cancer, [11] ovarian clear cell carcinoma, [12] liver cancer, [13] lymphoma [14] and pancreatic cancer. [15] In breast cancer distant metastases acquire inactivation mutations in ARID1A not seen in the primary tumor, and reduced ARID1A expression confers resistance to different drugs such as trastuzumab and mTOR inhibitors. These findings provide a rationale for why tumors accumulate ARID1A mutations. [16] [17]
Lack of this gene/protein seems to protect rats from some types of liver damage. [18]
ARID1A has been shown to interact with SMARCB1 [19] [20] and SMARCA4. [20] [21]
RSC is a member of the ATP-dependent chromatin remodeler family. The activity of the RSC complex allows for chromatin to be remodeled by altering the structure of the nucleosome.
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.
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.
DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that is encoded by the POLR2A gene in humans.
Transcription activator BRG1 also known as ATP-dependent chromatin remodeler SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a protein that in humans is encoded by the SMARCB1 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.
SWI/SNF complex subunit SMARCC1 is a protein that in humans is encoded by the SMARCC1 gene.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 is a protein that in humans is encoded by the SMARCE1 gene.
SWI/SNF complex subunit SMARCC2 is a protein that in humans is encoded by the SMARCC2 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.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 is a protein that in humans is encoded by the SMARCD1 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.
AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 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.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 2 is a protein that in humans is encoded by the SMARCD2 gene.
In molecular biology, the ARID domain ) is a protein domain that binds to DNA. ARID domain-containing proteins are found in fungi, plants and invertebrate and vertebrate metazoans. ARID-encoding genes are involved in a variety of biological processes including embryonic development, cell lineage gene regulation and cell cycle control. Although the specific roles of this domain and of ARID-containing proteins in transcriptional regulation are yet to be elucidated, they include both positive and negative transcriptional regulation and a likely involvement in the modification of chromatin structure. The basic structure of the ARID domain appears to be a series of six alpha-helices separated by beta-strands, loops, or turns, but the structured region may extend to an additional helix at either or both ends of the basic six. Based on primary sequence homology, they can be partitioned into three structural classes: Minimal ARID proteins that consist of a core domain formed by six alpha helices; ARID proteins that supplement the core domain with an N-terminal alpha-helix; and Extended-ARID proteins, which contain the core domain and additional alpha-helices at their N- and C-termini.
Diana Hargreaves is an American biologist and assistant professor at The Salk Institute for Biological Studies and member of The Salk Cancer Center. Her laboratory focuses on epigenetic regulation by the BAF (SWI/SNF) chromatin remodeling complexes in diverse physiological processes including development, immunity, and diseases such as cancer.
Robert E. Kingston is an American biochemist who studies the functional and regulatory role nucleosomes play in gene expression, specifically during early development. After receiving his PhD (1981) and completing post-doctoral research, Kingston became an assistant professor at Massachusetts General Hospital (1985), where he started a research laboratory focused on understanding chromatin's structure with regards to transcriptional regulation. As a Harvard graduate himself, Kingston has served his alma mater through his leadership.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
