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Background  Alterations in brain-derived neurotrophic factor ( BDNF ) gene expression contribute to serious pathologies such as depression, epilepsy, cancer, Alzheimer's, Huntington and Parkinson's disease. Therefore, exploring the mechanisms of  BDNF  regulation represents a great clinical importance. Studying  BDNF  expression remains difficult due to its multiple neural activity-dependent and tissue-specific promoters. Thus, microarray data could provide insight into the regulation of this complex gene. Conventional microarray co-expression analysis is usually carried out by merging the datasets or by confirming the re-occurrence of significant correlations across datasets. However, co-expression patterns can be different under various conditions that are represented by subsets in a dataset. Therefore, assessing co-expression by measuring correlation coefficient across merged samples of a dataset or by merging datasets might not capture all correlation patterns.    Results  In our study, we performed meta-coexpression analysis of publicly available microarray data using  BDNF  as a "guide-gene" introducing a "subset" approach. The key steps of the analysis included: dividing datasets into subsets with biologically meaningful sample content (e.g. tissue, gender or disease state subsets); analyzing co-expression with the  BDNF  gene in each subset separately; and confirming co- expression links across subsets. Finally, we analyzed conservation in co-expression with  BDNF  between human, mouse and rat, and sought for conserved over-represented TFBSs in  BDNF  and BDNF-correlated genes. Correlated genes discovered in this study regulate nervous system development, and are associated with various types of cancer and neurological disorders. Also, several transcription factor identified here have been reported to regulate  BDNF  expression  in vitro  and  in vivo .    Conclusion  The study demonstrates the potential of the "subset" approach in co-expression conservation analysis for studying the regulation of single genes and proposes novel regulators of  BDNF  gene expression.

Meta-coexpression conservation analysis of microarray data: a "subset" approach provides insight into brain-derived neurotrophic factor regulation