Computational identification of potential transcriptional regulators of TGF-ß1 in human atherosclerotic arteries

• Small clusters of co-expressed genes are helpful to study expression regulation.
• A set of transcription factors (TFs) may regulate TGFB1 in human atherosclerosis.
• Several TFs not detected in cancers may be specific of early atherosclerosis.
• Some known TFs but not co-expressed with TGFB1 could regulate its basal expression.
• Some TFs co-expressed with the TFGB1 cluster could fine-tune the TGFB1 expression.

TGF-ß is protective in atherosclerosis but deleterious in metastatic cancers. Our aim was to determine whether TGF-ß transcriptional regulation is tissue-specific in early atherosclerosis. The computational methods included 5 steps: (i) from microarray data of human atherosclerotic carotid tissue, to identify the 10 best co-expressed genes with TGFB1 (TGFB1 gene cluster), (ii) to choose the 11 proximal promoters, (iii) to predict the TFBS shared by the promoters, (iv) to identify the common TFs co-expressed with the TGFB1 gene cluster, and (v) to compare the common TFs in the early lesions to those identified in advanced atherosclerotic lesions and in various cancers. Our results show that EGR1, SP1 and KLF6 could be responsible for TGFB1 basal expression, KLF6 appearing specific to atherosclerotic lesions. Among the TFs co-expressed with the gene cluster, transcriptional activators (SLC2A4RG, MAZ) and repressors (ZBTB7A, PATZ1, ZNF263) could be involved in the fine-tuning of TGFB1 expression in atherosclerosis.