Mastitis is one of the costliest diseases in dairy farms caused by infection of different microorganisms such as
Escherichia coli, Streptococcus uberis and Staphylococcus aureus. Promoters are significantly involved in regulating
gene expression and shedding light on the mechanisms of transcriptional regulation in physiological and
immunological processes of the infections. Exploiting regulatory elements such as transcription factor binding
sites (TFBSs modules) on the promoter region could reveal co-regulated genes, which allow screating regulatory
models and executing a cross-sectional analysis on several databases. In this study, the promoter regions of 11
genes associated with contagious mastitis including CCL4, CXCL8, STAT3, IKBKB, MAPK14, NFKBIA, NFKB1,
TNF, IL18, IL6, and HCK were investigated to predict the activating regulatory modules on promoters and to
discover the key related transcription factors. By exploring the promoter regions, 228 genes were discovered
comprising the same transcription factors modules. Out of 228 genes, 36 were validated using five microarray
datasets. The promoter research of these genes revealed that as many as 7 down-regulated and 12 up-regulated
genes are predictable in the network. The genes whose functions were associated with the initial gene list (11
genes), were identified by DAVID queries with TFBSs models implying that the approach provides a clear image
of the underlying regulatory mechanism of gene expression profile and offers a novel approach in designing gene
networks in cattle.