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The BCL2 major breakpoint region (mbr) regulates gene expression

Oncogene volume 26, pages 2649–2657 (2007)Cite this article

Abstract

BCL2 expression is finely tuned by a variety of environmental and endogenous stimuli and regulated at both transcriptional and post-transcriptional levels. Our previous investigations demonstrated that the BCL2 major breakpoint region (mbr) in the 3′-UTR upregulates reporter gene expression, which implies that this region possessed intrinsic regulatory function. However, the effect of the mbr on BCL2 expression, and the underlying regulatory mechanisms, remain to be elucidated. To assess the direct effect of the mbr on the transcriptional activity of the BCL2 gene, we employed targeted homologous recombination to establish a mbr+/mbr− heterozygous Nalm-6 cell line and then compared the transcriptional activity and apoptotic effect on transcription between the wild type and targeted alleles. We found that deletion of the mbr significantly decreased the transcriptional activity of the corresponding allele in the mbr+/mbr− cell. The BCL2 allele deleted of the mbr had a slower response to apoptotic stimuli than did the wild type allele. The regulatory function of the mbr was mediated through SATB1. Overexpression of SATB1 increased BCL2 expression, while knockdown of SATB1 with RNAi decreased BCL2 expression. Our results clearly indicated that the mbr could positively regulate BCL2 gene expression and this regulatory function was closely related to SATB1.

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Abbreviations

mbr:

major breakpoint region

SATB1:

special AT-rich sequence-binding protein 1

MAR:

matrix attachment region

CRE:

cAMP responsive element

NF-κB:

nuclear factor-kappa B

UTR:

untranslated region

EMSA:

electrophoretic mobility shift assay

DT:

diphtheria-toxin

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Acknowledgements

We thank Dr Krontiris for his kind help in this work. This work was supported by grants from the National Natural Science Foundation of China (30371592), the Nature Science Foundation of Jiangsu Province (BK2003003), the Special Funds for Major State Basic Research Program of China (973 Program, 2006CB503908) and Opening Foundation from Jiangsu key laboratory for molecular and medical biotechnology.

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Authors and Affiliations

  1. Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, PR China

    C Ma, J Zhang, J Lv, X Han & Y Sun

  2. Department of Cell Biology and Medical Genetics, Nanjing Medical University, Nanjing, PR China

    C Ma & Y Sun

  3. School of Pharmacy, Nanjing Medical University, Nanjing, PR China

    D Zhu

  4. Department of Molecular Medicine, City of Hope National Medical Center, Duarte, CA, USA

    L K Durrin

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  1. C Ma
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Correspondence to X Han or Y Sun.

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Ma, C., Zhang, J., Durrin, L. et al. The BCL2 major breakpoint region (mbr) regulates gene expression. Oncogene 26, 2649–2657 (2007). https://doi.org/10.1038/sj.onc.1210069

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