Essential Role of ARID2 Protein-containing SWI/SNF Complex in Tissue-specific Gene Expression

Xu, Fusheng; Flowers, Stephen; Morán, Elizabeth

doi:10.1074/jbc.m111.279968

Cited by 65 publications

(62 citation statements)

References 52 publications

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“…ARID2 plays an essential role in osteoblast differentiation using MC3T3-E1 pre-osteoblasts as a model. ARID2-depletion severely impaired the mature mineralization of osteoblasts [38]. ARID2 is found in the multiple protein complex that participates in SRF-dependent gene regulation, and affects the promoter activity of cardiac genes in NIH3T3 cells [27].…”

Section: Resultsmentioning

confidence: 99%

Mutations in ARID2 are associated with intellectual disabilities

Shang

Cho²,

Retterer³

et al. 2015

Neurogenetics

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The etiology of intellectual disabilities (ID) remains unknown for the majority of patients. Due to reduced reproductive fitness in many individuals with ID, de novo mutations account for a significant portion of severe ID. The ATP-dependent SWI/SNF chromatin modifier has been linked with neurodevelopmental disorders including ID and autism. ARID2 is an intrinsic component of polybromo-associated BAF (PBAF), the SWI/SNF subcomplex. In this study, we used clinical whole exome sequencing (WES) in proband-parent-trios to identify the etiology of ID. We identified four independent, novel, loss of function variants in ARID2 gene in four patients, three of which were confirmed to be de novo. The patients all have ID and share other clinical characteristics including attention deficit hyperactivity disorder, short stature, dysmorphic facial features, and Wormian bones. All four novel variants are predicted to lead to a premature termination with the loss of the two conservative zinc finger motifs. This is the first report of mutations in ARID2 associated with developmental delay and ID.

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Section: Resultsmentioning

confidence: 99%

Mutations in ARID2 are associated with intellectual disabilities

Shang

Cho²,

Retterer³

et al. 2015

Neurogenetics

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“…PBAF subunits regulate cell differentiation and may be an important regulator of cell-type identity (Bajpai et al 2010; Xu et al 2012). Additionally, a large body of evidence shows that PBAF complexes have important roles in the maintenance of genomic integrity during mitosis, described in more detail below (see “Non-transcriptional roles of BAF/PBAF complexes in cancer ”) .…”

Section: Baf and Pbaf In Mammalsmentioning

confidence: 99%

The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer

Hodges

Kirkland

Crabtree

2016

Cold Spring Harb Perspect Med

343

294

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During the last decade, a host of epigenetic mechanisms were found to contribute to cancer and other human diseases. Several genomic studies have revealed that ~20% of malignancies have alterations of the subunits of polymorphic BAF and PBAF complexes, making them among the most frequently mutated complexes in cancer. Recurrent mutations arise in genes encoding several BAF/PBAF subunits, including ARID1A, ARID2, PBRM1, SMARCA4, and SMARCB1. These subunits share some degree of conservation with subunits from related ATP-dependent chromatin remodeling complexes in model organisms, where a large body of work provides insight into their roles in cancer. Here we review the roles of BAF- and PBAF-like complexes in these organisms, and relate these findings to recent discoveries in cancer epigenomics. We review several roles of BAF and PBAF complexes in cancer, including transcriptional regulation, DNA repair, and regulation of chromatin architecture and topology. More recent results highlight the need for new techniques to study these complexes.

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“…Quantitative reverse transcription PCR (qRT-PCR) was conducted as described previously with the Alpl , Bglap , Rb1 and Gapdh expression primers (17, 23, 46). Other primers used were: p107 (Forward 5′ AGG AAG TTC GCA CTG ACA GTG G- 3′; Reverse 5′-CAG TCT CCT CTT AGC and OPN (Forward 5′-GCT TGG CTT ATG GAC TGA GGT C- 3′ and Reverse 5′-CCT TAG ACT CAC CGC TCT TCA TG).…”

Section: Methodsmentioning

confidence: 99%

p107-Dependent recruitment of SWI/SNF to the alkaline phosphatase promoter during osteoblast differentiation

Flowers

Patel

Gleicher

et al. 2014

Bone

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The retinoblastoma protein family is intimately involved in the regulation of tissue specific gene expression during mesenchymal stem cell differentiation. The role of these proteins, pRB, p107 and p130, is particularly significant in differentiation to the osteoblast lineage, as human germ-line mutations of RB1 greatly increase susceptibility to osteosarcoma. During differentiation, pRB directly targets certain osteogenic genes for activation, including the alkaline phosphatase-encoding gene Alpl. Chromatin immunoprecipitation (ChIP) assays indicate Alpl is targeted by p107 in differentiating osteoblasts selectively during activation with the same dynamics as pRB, which suggests that p107 helps promote Alpl activation. Mouse models indicate overlapping roles for pRB and p107 in bone and cartilage formation, but very little is known about direct tissue-specific gene targets of p107, or the consequences of targeting by p107. Here, the roles of p107 and pRB were compared using shRNA-mediated knockdown genetics in an osteoblast progenitor model, MC3T3-E1 cells. The results show that p107 has a distinct role along with pRB in induction of Alpl. Deficiency of p107 does not impede recruitment of transcription factors recognized as pRB co-activation partners at the promoter; however, p107 is required for efficient recruitment of an activating SWI/SNF chromatin-remodeling complex, an essential event in Alpl induction.

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Essential Role of ARID2 Protein-containing SWI/SNF Complex in Tissue-specific Gene Expression

Cited by 65 publications

References 52 publications

Mutations in ARID2 are associated with intellectual disabilities

Mutations in ARID2 are associated with intellectual disabilities

The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer

p107-Dependent recruitment of SWI/SNF to the alkaline phosphatase promoter during osteoblast differentiation

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