ARID1A explained

AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.^{[1] [2] [3]}

Function

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.^[4] Two transcript variants encoding different isoforms have been found for this gene.^[3]

Clinical significance

Gene encoding for ARID1A is the most frequently mutated SWI/SNF subunit across cancers.^[5] This gene has been commonly found mutated in different cancers leading to loss of function, including gastric cancers,^[6] colon cancer,^[7] ovarian clear cell carcinoma,^[8] liver cancer,^[9] lymphoma^[10] and pancreatic cancer.^[11] 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.^{[12] [13]}

Research

Lack of this gene/protein seems to protect rats from some types of liver damage.^[14]

Interactions

ARID1A has been shown to interact with SMARCB1^{[15] [16]} and SMARCA4.^{[16] [17]}

Further reading

• Martens JA, Winston F . Recent advances in understanding chromatin remodeling by Swi/Snf complexes . Current Opinion in Genetics & Development . 13 . 2 . 136–142 . April 2003 . 12672490 . 10.1016/S0959-437X(03)00022-4 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Wang W, Xue Y, Zhou S, Kuo A, Cairns BR, Crabtree GR . Diversity and specialization of mammalian SWI/SNF complexes . Genes & Development . 10 . 17 . 2117–2130 . September 1996 . 8804307 . 10.1101/gad.10.17.2117 . free .
• Wang W, Côté J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL, Crabtree GR . Purification and biochemical heterogeneity of the mammalian SWI-SNF complex . The EMBO Journal . 15 . 19 . 5370–5382 . October 1996 . 8895581 . 452280 . 10.1002/j.1460-2075.1996.tb00921.x .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Dallas PB, Cheney IW, Liao DW, Bowrin V, Byam W, Pacchione S, Kobayashi R, Yaciuk P, Moran E . p300/CREB binding protein-related protein p270 is a component of mammalian SWI/SNF complexes . Molecular and Cellular Biology . 18 . 6 . 3596–3603 . June 1998 . 9584200 . 108941 . 10.1128/MCB.18.6.3596 .
• Dallas PB, Pacchione S, Wilsker D, Bowrin V, Kobayashi R, Moran E . The human SWI-SNF complex protein p270 is an ARID family member with non-sequence-specific DNA binding activity . Molecular and Cellular Biology . 20 . 9 . 3137–3146 . May 2000 . 10757798 . 85608 . 10.1128/MCB.20.9.3137-3146.2000 .
• Nie Z, Xue Y, Yang D, Zhou S, Deroo BJ, Archer TK, Wang W . A specificity and targeting subunit of a human SWI/SNF family-related chromatin-remodeling complex . Molecular and Cellular Biology . 20 . 23 . 8879–8888 . December 2000 . 11073988 . 86543 . 10.1128/MCB.20.23.8879-8888.2000 .
• Takeuchi T, Nicole S, Misaki A, Furihata M, Iwata J, Sonobe H, Ohtsuki Y . Expression of SMARCF1, a truncated form of SWI1, in neuroblastoma . The American Journal of Pathology . 158 . 2 . 663–672 . February 2001 . 11159203 . 1850330 . 10.1016/S0002-9440(10)64008-4 .
• Kozmik Z, Machon O, Králová J, Kreslová J, Paces J, Vlcek C . Characterization of mammalian orthologues of the Drosophila osa gene: cDNA cloning, expression, chromosomal localization, and direct physical interaction with Brahma chromatin-remodeling complex . Genomics . 73 . 2 . 140–148 . April 2001 . 11318604 . 10.1006/geno.2001.6477 .
• Kato H, Tjernberg A, Zhang W, Krutchinsky AN, An W, Takeuchi T, Ohtsuki Y, Sugano S, de Bruijn DR, Chait BT, Roeder RG . SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones . The Journal of Biological Chemistry . 277 . 7 . 5498–5505 . February 2002 . 11734557 . 10.1074/jbc.M108702200 . free . free . 2066/170683 .
• Lemon B, Inouye C, King DS, Tjian R . Selectivity of chromatin-remodelling cofactors for ligand-activated transcription . Nature . 414 . 6866 . 924–928 . 2002 . 11780067 . 10.1038/414924a . 4391100 .
• Hurlstone AF, Olave IA, Barker N, van Noort M, Clevers H . Cloning and characterization of hELD/OSA1, a novel BRG1 interacting protein . The Biochemical Journal . 364 . Pt 1 . 255–264 . May 2002 . 11988099 . 1222568 . 10.1042/bj3640255 .
• Inoue H, Furukawa T, Giannakopoulos S, Zhou S, King DS, Tanese N . Largest subunits of the human SWI/SNF chromatin-remodeling complex promote transcriptional activation by steroid hormone receptors . The Journal of Biological Chemistry . 277 . 44 . 41674–41685 . November 2002 . 12200431 . 10.1074/jbc.M205961200 . free .
• Nie Z, Yan Z, Chen EH, Sechi S, Ling C, Zhou S, Xue Y, Yang D, Murray D, Kanakubo E, Cleary ML, Wang W . Novel SWI/SNF chromatin-remodeling complexes contain a mixed-lineage leukemia chromosomal translocation partner . Molecular and Cellular Biology . 23 . 8 . 2942–2952 . April 2003 . 12665591 . 152562 . 10.1128/MCB.23.8.2942-2952.2003 .

Notes and References

1. Takeuchi T, Furihata M, Heng HH, Sonobe H, Ohtsuki Y . Chromosomal mapping and expression of the human B120 gene . Gene . 213 . 1–2 . 189–193 . June 1998 . 9630625 . 10.1016/S0378-1119(98)00194-2 .
2. Takeuchi T, Chen BK, Qiu Y, Sonobe H, Ohtsuki Y . Molecular cloning and expression of a novel human cDNA containing CAG repeats . Gene . 204 . 1–2 . 71–77 . December 1997 . 9434167 . 10.1016/S0378-1119(97)00525-8 .
3. Web site: Entrez Gene: ARID1A AT rich interactive domain 1A (SWI-like).
4. Patil A, Strom AR, Paulo JA, Collings CK, Ruff KM, Shinn MK, Sankar A, Cervantes KS, Wauer T, St Laurent JD, Xu G, Becker LA, Gygi SP, Pappu RV, Brangwynne CP, Kadoch C . A disordered region controls cBAF activity via condensation and partner recruitment . Cell . 186 . 22 . 4936–4955.e26 . October 2023 . 37788668 . 10792396 . 10.1016/j.cell.2023.08.032 . October 26, 2024 .
5. Gourisankar S, Krokhotin A, Wenderski W, Crabtree GR . Context-specific functions of chromatin remodellers in development and disease . Nature Reviews. Genetics . 340–361 . November 2023 . 25 . 5 . 38001317 . 10.1038/s41576-023-00666-x .
6. Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, Chan TL, Kan Z, Chan AS, Tsui WY, Lee SP, Ho SL, Chan AK, Cheng GH, Roberts PC, Rejto PA, Gibson NW, Pocalyko DJ, Mao M, Xu J, Leung SY . Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer . Nature Genetics . 43 . 12 . 1219–1223 . October 2011 . 22037554 . 10.1038/ng.982 . 8884065 .
7. Mathur R, Alver BH, San Roman AK, Wilson BG, Wang X, Agoston AT, Park PJ, Shivdasani RA, Roberts CW . ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice . Nature Genetics . 49 . 2 . 296–302 . February 2017 . 27941798 . 5285448 . 10.1038/ng.3744 .
8. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih I, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG . ARID1A mutations in endometriosis-associated ovarian carcinomas . The New England Journal of Medicine . 363 . 16 . 1532–1543 . October 2010 . 20942669 . 2976679 . 10.1056/NEJMoa1008433 .
9. Sun X, Wang SC, Wei Y, Luo X, Jia Y, Li L, Gopal P, Zhu M, Nassour I, Chuang JC, Maples T, Celen C, Nguyen LH, Wu L, Fu S, Li W, Hui L, Tian F, Ji Y, Zhang S, Sorouri M, Hwang TH, Letzig L, James L, Wang Z, Yopp AC, Singal AG, Zhu H . Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer . Cancer Cell . 32 . 5 . 574–589.e6 . November 2017 . 29136504 . 5728182 . 10.1016/j.ccell.2017.10.007 .
10. Barisic D, Chin CR, Meydan C, Teater M, Tsialta I, Mlynarczyk C, Chadburn A, Wang X, Sarkozy M, Xia M, Carson SE, Raggiri S, Debek S, Pelzer B, Durmaz C, Deng Q, Lakra P, Rivas M, Steidl C, Scott DW, Weng AP, Mason CE, Green MR, Melnick A . ARID1A orchestrates SWI/SNF-mediated sequential binding of transcription factors with ARID1A loss driving pre-memory B cell fate and lymphomagenesis . Cancer Cell . March 2024 . 42 . 4 . 583–604.e11 . 38458187 . 10.1016/j.ccell.2024.02.010 .
11. Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M, Maitra A, Pollack JR . Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer . Proceedings of the National Academy of Sciences of the United States of America . 109 . 5 . E252–E259 . January 2012 . 22233809 . 3277150 . 10.1073/pnas.1114817109 . free .
12. Berns K, Sonnenblick A, Gennissen A, Brohée S, Hijmans EM, Evers B, Fumagalli D, Desmedt C, Loibl S, Denkert C, Neven P, Guo W, Zhang F, Knijnenburg TA, Bosse T, van der Heijden MS, Hindriksen S, Nijkamp W, Wessels LF, Joensuu H, Mills GB, Beijersbergen RL, Sotiriou C, Bernards R . Loss of ARID1A Activates ANXA1, which Serves as a Predictive Biomarker for Trastuzumab Resistance . Clinical Cancer Research . 22 . 21 . 5238–5248 . November 2016 . 27172896 . 10.1158/1078-0432.CCR-15-2996 . free .
13. Yates LR, Knappskog S, Wedge D, Farmery JH, Gonzalez S, Martincorena I, Alexandrov LB, Van Loo P, Haugland HK, Lilleng PK, Gundem G, Gerstung M, Pappaemmanuil E, Gazinska P, Bhosle SG, Jones D, Raine K, Mudie L, Latimer C, Sawyer E, Desmedt C, Sotiriou C, Stratton MR, Sieuwerts AM, Lynch AG, Martens JW, Richardson AL, Tutt A, Lønning PE, Campbell PJ . Genomic Evolution of Breast Cancer Metastasis and Relapse . Cancer Cell . 32 . 2 . 169–184.e7 . August 2017 . 28810143 . 5559645 . 10.1016/j.ccell.2017.07.005 .
14. Web site: Tissue Regeneration Promoted through Gene Suppression . March 2016 . Genetic Engineering & Biotechnology News .
15. Kato H, Tjernberg A, Zhang W, Krutchinsky AN, An W, Takeuchi T, Ohtsuki Y, Sugano S, de Bruijn DR, Chait BT, Roeder RG . SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones . The Journal of Biological Chemistry . 277 . 7 . 5498–5505 . February 2002 . 11734557 . 10.1074/jbc.M108702200 . free . free . 2066/170683 .
16. Wang W, Côté J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL, Crabtree GR . Purification and biochemical heterogeneity of the mammalian SWI-SNF complex . The EMBO Journal . 15 . 19 . 5370–5382 . October 1996 . 8895581 . 452280 . 10.1002/j.1460-2075.1996.tb00921.x .
17. Zhao K, Wang W, Rando OJ, Xue Y, Swiderek K, Kuo A, Crabtree GR . Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling . Cell . 95 . 5 . 625–636 . November 1998 . 9845365 . 10.1016/S0092-8674(00)81633-5 . 3184211 . free .