Alternative titles; symbols
HGNC Approved Gene Symbol: ARID3A
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:925,732-975,939 (from NCBI)
ARID3A is a transcriptional activator that functions in concert with Gata1 (305371) to promote terminal megakaryocytic differentiation (Alejo-Valle et al., 2022).
Herrscher et al. (1995) identified the mouse Bright (B-cell regulator of IgH transcription) gene. They found that the Bright protein is expressed specifically in B cells and transactivates an IgH enhancer in transient transfection assays. Bright and the Drosophila 'dead ringer' (dri) gene product belong to a protein family whose members share a conserved DNA-binding domain termed the 'A/T-rich interaction domain' (ARID).
By PCR using degenerate primers based on the ARID sequence, Kortschak et al. (1998) isolated a HeLa cell cDNA encoding DRIL1. Overall, the predicted protein is 79% identical to mouse Bright. The DNA-binding domain of DRIL1 is highly conserved, sharing 97% and 79% identity with the DNA-binding domain of Bright and DRI, respectively. Northern and dot blot analyses revealed that DRIL1 was expressed as a 4.4-kb mRNA in all tissues tested.
Patsialou et al. (2005) noted that members of the ARID3 family have a conserved 35-residue region called the extended ARID domain immediately following the core ARID domain. They analyzed DNA binding properties of all members of the ARID family using GST fusion proteins. ARID3A selectively bound to AT-rich sites.
Ratliff et al. (2015) had previously shown that numbers of ARID3A-positive B cells were increased in many patients with systemic lupus erythematosus (SLE; 152700), and that total numbers of ARID3A-positive B cells were associated with increased disease severity. Using flow cytometric analysis, Ratliff et al. (2015) demonstrated that ARID3A was not limited to any defined subset of hemopoietic stem/progenitor cells (HSPCs) in either healthy controls or SLE patients. Numbers of ARID3A-positive HSPCs in SLE patients were increased compared with numbers of ARID3A-positive cells in healthy controls. Although SLE-derived HSPCs showed poor colony formation in vitro, SLE HSPCs with high numbers of ARID3A-positive cells yielded increased numbers of cells expressing the early progenitor marker CD34 (142230). Moreover, SLE HSPCs with high numbers of ARID3A-positive cells more readily generated autoantibody-producing cells than HSPCs with lower ARID3A levels in a humanized mouse model.
Using a knockdown screen, Alejo-Valle et al. (2022) identified Arid3a as a target of chromosome 21-encoded miR125b (MIR125B2; 610105) that worked in synergy with Gata1 mutations in fetal liver cells to cause megakaryocytic leukemia in a mouse model. Knockdown and overexpression analyses in HSPCs revealed that Arid3a functioned as a transcriptional activator in concert with Gata1 to activate megakaryocytic transcriptional programs to promote terminal megakaryocytic differentiation. Arid3a interacted directly with Smad2 (601366) and Smad3 (603109) and promoted activation of the Tgf-beta (TGFB1; 190180) pathway. ARID3A expression was reduced in blasts from patients with acute megakaryoblastic leukemia, and restoring ARID3A expression reestablished normal differentiation.
Kortschak et al. (1998) determined that the ARID3A gene contains 8 exons.
Kortschak et al. (1998) mapped the ARID3A gene to chromosome 19p13.3 by fluorescence in situ hybridization and by analysis of cosmids from this region.
Alejo-Valle, O., Weigert, K., Bhayadia, R., Ng, M., Issa, H., Beyer, C., Emmrich, S., Schuschel, K., Ihling, C., Sinz, A., Zimmermann, M., Wickenhauser, C., Flasinski, M., Regenyi, E., Labuhn, M., Reinhardt, D., Yaspo, M. L., Heckl, D., Klusmann, J. H. The megakaryocytic transcription factor ARID3A suppresses leukemia pathogenesis. Blood 139: 651-665, 2022. [PubMed: 34570885] [Full Text: https://doi.org/10.1182/blood.2021012231]
Herrscher, R. F., Kaplan, M. H., Lelsz, D. L., Das, C., Scheuermann, R., Tucker, P. W. The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a B cell-specific trans-activator that describes a new DNA-binding protein family. Genes Dev. 9: 3067-3082, 1995. [PubMed: 8543152] [Full Text: https://doi.org/10.1101/gad.9.24.3067]
Kortschak, R. D., Reimann, H., Zimmer, M., Eyre, H. J., Saint, R., Jenne, D. E. The human dead ringer/bright homolog, DRIL1: cDNA cloning, gene structure, and mapping to D19S886, a marker on 19p13.3 that is strictly linked to the Peutz-Jeghers syndrome. Genomics 51: 288-292, 1998. [PubMed: 9722953] [Full Text: https://doi.org/10.1006/geno.1998.5259]
Patsialou, A., Wilsker, D., Moran, E. DNA-binding properties of ARID family proteins. Nucleic Acids Res. 33: 66-80, 2005. [PubMed: 15640446] [Full Text: https://doi.org/10.1093/nar/gki145]
Ratliff, M. L., Ward, J. M., Merrill, J. T., James, J. A., Webb, C. F. Differential expression of the transcription factor ARID3a in lupus patient hematopoietic progenitor cells. J. Immun. 194: 940-949, 2015. [PubMed: 25535283] [Full Text: https://doi.org/10.4049/jimmunol.1401941]