Two related ARID family proteins are alternative subunits of human SWI/SNF complexes

Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Biochemical Journal (Impact Factor: 4.78). 11/2004; 383(Pt 2):319-25. DOI: 10.1042/BJ20040524
Source: PubMed

ABSTRACT p270 (ARID1A) is a member of the ARID family of DNA-binding proteins and a subunit of human SWI/SNF-related complexes, which use the energy generated by an integral ATPase subunit to remodel chromatin. ARID1B is an independent gene product with an open reading frame that is more than 60% identical with p270. We have generated monoclonal antibodies specific for either p270 or ARID1B to facilitate the investigation of ARID1B and its potential interaction with human SWI/SNF complexes in vivo. Immunocomplex analysis provides direct evidence that endogenous ARID1B is associated with SWI/SNF-related complexes and indicates that p270 and ARID1B, similar to the ATPase subunits BRG1 and hBRM, are alternative, mutually exclusive subunits of the complexes. The ARID-containing subunits are not specific to the ATPases. Each associates with both BRG1 and hBRM, thus increasing the number of distinct subunit combinations known to be present in cells. Analysis of the panels of cell lines indicates that ARID1B, similar to p270, has a broad tissue distribution. The ratio of p270/ARID1B in typical cells is approx. 3.5:1, and BRG1 is distributed proportionally between the two ARID subunits. Analysis of DNA-binding behaviour indicates that ARID1B binds DNA in a non-sequence-specific manner similar to p270.

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Available from: Peter Dallas, Nov 10, 2014
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    • "ARID1A is located within chromosomal region 1p36, a region frequently deleted in a variety of human neoplastic diseases [8]. ARID1A encodes a large nuclear protein that interacts with several other proteins including either BRG or BRM, ATPases that participate in the formation of a switch/sucrose non fermentable (SMI/SNF) chromatin remodeling complex [9] [10]. BAF250a, the protein encoded by ARID1A, is one of the accessory subunits of the SWI/SNF complex. "
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    ABSTRACT: Loss of the AT-rich interactive domain 1A (a putative tumor suppressor) protein BAF250a has recently been described as a frequent event in endometrial carcinoma. In this study, we determined the significance of the loss of AT-rich interactive domain 1A immunoreactivity for several clinicopathologic features of uterine endometrioid carcinoma. AT-rich interactive domain 1A expression was assessed by immunohistochemistry using 111 paraffin-embedded tissue specimens and clinical data collected by a retrospective medical record review. The correlations between loss of AT-rich interactive domain 1A protein and clinicopathologic and prognostic features were examined. In addition, the expression of PTEN, p53, Her2, and MLH1 was assessed by immunohistochemistry and compared with AT-rich interactive domain 1A expression. AT-rich interactive domain 1A immunoreactivity was undetectable in 27 (24%) of 111 analyzed endometrioid endometrial carcinomas. There was no significant difference between negative and positive cases of AT-rich interactive domain 1A in terms of any clinicopathologic features examined (International Federation of Gynecology and Obstetrics stage, grade, depth of myometrial invasion, lymph node metastasis, lymphovascular space invasion, body mass index, postmenopausal status, patient age at diagnosis, and estrogen and progesterone receptor status). The comparison between the expression of AT-rich interactive domain 1A and the expression of PTEN, p53, Her2, and MLH1 also revealed no significant association. There was no significant correlation between AT-rich interactive domain 1A expression and progression-free/overall survival of patients. This study provides the first examination of the clinicopathologic relationship between AT-rich interactive domain 1A protein expression and endometrial carcinoma. No significant differences between positive and negative cases of AT-rich interactive domain 1A were observed with respect to any clinicopathologic features or patient survival.
    Human pathology 08/2012; 44(1). DOI:10.1016/j.humpath.2012.04.021 · 2.81 Impact Factor
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    • "The protein encoded by ARID1A is a key component of the highly conserved SWI–SNF (switch/sucrose non-fermentable) chromatin remodeling complex that uses adenosine triphosphate (ATP)dependent helicase activities to allow access of transcriptional activators and repressors to DNA [Wang et al., 2004; Wilson and Roberts, 2011]. The protein therefore appears to be involved in regulating processes including DNA repair, differentiation, and development [Weissman et al., 2009]. "
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    ABSTRACT: Mutations in the chromatin remodeling gene ARID1A have recently been identified in the majority of ovarian clear cell carcinomas (OCCCs). To determine the prevalence of mutations in other tumor types, we evaluated 759 malignant neoplasms including those of the pancreas, breast, colon, stomach, lung, prostate, brain, and blood (leukemias). We identified truncating mutations in 6% of the neoplasms studied; nontruncating somatic mutations were identified in an additional 0.4% of neoplasms. Mutations were most commonly found in gastrointestinal samples with 12 of 119 (10%) colorectal and 10 of 100 (10%) gastric neoplasms, respectively, harboring changes. More than half of the mutated colorectal and gastric cancers displayed microsatellite instability (MSI) and the mutations in these tumors were out-of-frame insertions or deletions at mononucleotide repeats. Mutations were also identified in 2-8% of tumors of the pancreas, breast, brain (medulloblastomas), prostate, and lung, and none of these tumors displayed MSI. These findings suggest that the aberrant chromatin remodeling consequent to ARID1A inactivation contributes to a variety of different types of neoplasms.
    Human Mutation 01/2012; 33(1):100-3. DOI:10.1002/humu.21633 · 5.05 Impact Factor
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    • "Two different genes encode BAF250 proteins. BAF250A (also known as OSA1 and p270/ARID1A) is encoded by ARID1A, whereas BAF250B (OSA2) is encoded by ARID1B (Hurlstone et al., 2002; Wang et al., 2004b). In addition to the ARID domains, BAF250s also contain EHD1 and EHD2 domains, which map to the C termini and mediate protein binding (Hurlstone et al., 2002). "
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