Accurate Identification of BIK Binding Sites at the MDA-MB-231 Cell Genome by Human Tiling Arrays

Background:
BIK (BCL2-Interacting Killer (Apoptosis-Inducing)) is a multifaceted protein which has gained importance in the study of cancer, particularly in breast cancer. It was recently demonstrated its involvement in controlling the autophagy of the MDA-MB-231 autophagy-dependent cell line, as well as its location in the nucleus of these cells; however, the physiological meaning of this is unknown. Then, the objective of this work was to demonstrate the physical interaction of BIK with the MDA-MB-231 genome.

Methods and Findings:
We demonstrated BIK-DNA interactions by chip on chip. Tiling array analysis shows the interaction of BIK with coding and non-coding regions, mainly in chromosomes 1, 3, 6, and 22. PROMOTER 2.0 and GPMiner analyses demonstrated the interaction of BIK with promoters of specific genes, which, according to KEGG, are mainly involved in the control of metabolism, genetic information processing, signal transduction, cell growth and death, and drug resistance, among others. Importantly, BIK interference altered gene and microRNA expression.

Conclusion:
Our results showed, for the first time, the interaction of BIK with DNA, specifically with the MDA-MB-231 cells genome, which strongly suggests its involvement in the control of transcriptional expression of both coding and non-coding regions.

Author(s):   Ruiz Esparza-Garrido R, Ayala K , Torres-López J, Rodríguez-Corona JM and Velázquez-Flores MÁ*

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