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Diseases 2017, 5(4), 34; https://doi.org/10.3390/diseases5040034

Competitive Promoter-Associated Matrix Attachment Region Binding of the Arid3a and Cux1 Transcription Factors

1
Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78715, USA
2
Atreca, Inc., Redwood City, CA 94063, USA
3
Department of Biomaterials and Healthcare, Division of Life Science and Bioprocesses, Fraunhofer-Institute for Applied Polymer Research (IAP), 14476 Potsdam-Golm, Germany
4
Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA
*
Author to whom correspondence should be addressed.
Received: 15 November 2017 / Revised: 5 December 2017 / Accepted: 5 December 2017 / Published: 10 December 2017
(This article belongs to the Special Issue Pediatric Diseases)
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Abstract

Arid3a/Bright/Dril1 is a B cell-specific transactivator that regulates immunoglobulin heavy chain (IgH) gene transcription by binding promoter and enhancer-associated matrix attachment regions (MARs) within the IgH gene locus. Promoter MAR-mediated Arid3a transactivation is antagonized by direct competition of MAR binding by Cux1/CDP—a ubiquitously expressed repressor originally termed NF-μNR. We report that the NF-μNR complex includes Arid3a in B cells but not in non-B cells through mobility shift assays. The binding activity of NF-μNR and Arid3a in B cells is reciprocally altered during the cell division cycle and by the B cell mitogen lipopolysaccharide LPS. LPS treatment had no effect on Arid3a localization but increased its total abundance within the nucleus and cytoplasm. We show that this increased level of Arid3a is capable of displacing Cux from the MARs to facilitate IgH gene transcription. Finally, we showed that the MARs (termed Bf150 and Tx125) associated with the VH1 rearranged variable region expressed in the S107 murine plasmacytoma, can repress reporter gene transcription in non-B cells and that they can relieve the repression mediated by Eμ enhancer in B cells. These results have significant implications for early human development and demonstrate that MARs in IgH locus, NF-µNR and Arid3a regulate IgH gene expression in a concerted fashion. This paves the way for future studies examining the misregulation of this pathway in pediatric disease. View Full-Text
Keywords: immunoglobulin heavy chain; Arid3a; NF-µNR; matrix-attachment region (MAR); transactivation immunoglobulin heavy chain; Arid3a; NF-µNR; matrix-attachment region (MAR); transactivation
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Kim, D.; Schmidt, C.; Brown, M.A.; Tucker, H. Competitive Promoter-Associated Matrix Attachment Region Binding of the Arid3a and Cux1 Transcription Factors. Diseases 2017, 5, 34.

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