title: Functionally distinct gene classes as bigger or smaller transcription factor traps: a possible stochastic component to sequential gene expression programs in cancer.
abstract: In cancer biology, most molecular regulatory mechanisms are casually treated as on/off switches for specific cancer hallmarks, despite the lack of compelling evidence that cancer hallmarks can be exclusively attributed to specific regulatory proteins. To consider a novel paradigm for the basis of regulating a set of effector genes for proliferation, versus apoptosis-effector genes, we used a bioinformatics approach to ascertain differences between the transcription factor binding site occurrences in the two sets of genes. Results indicated that there are more binding sites per gene, for transcription factors that regulate both proliferation and apoptosis, among the proliferation-effector genes than among the apoptosis-effector genes. Proliferation-effector genes also had more open chromatin regions. We also applied this paradigm to the question of why p53 and interferon regulatory factor-1 (IRF-1) first activate cell cycle arrest genes followed by apoptosis genes, with results indicating the cycle arrest genes are bigger p53 and IRF-1 traps. These data support the idea that, as a set of transcription factors becomes active, there is a stochastic component leading to the accumulation of these transcription factors on genes that effect an initial phenotype before their accumulation on genes that effect a subsequent phenotype.
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Mauro
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States. Electronic address: gblanck@health.usf.edu.
authors.forename: George
authors.initials: G
authors.lastname: Blanck
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D020014:K562 Cells; D009369:Neoplasms / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53
keywords: Apoptosis; CIITA; Cell proliferation; ENCODE; Gene size; HS; IRF-1; MHC; NFAT; Open chromatin regions; SAHA; STAT; TF; TFBS; Transcription factors; YY1; Ying-Yang 1; class II transactivator; hypersensitive; interferon regulatory factor-1; major histocompatibility; nuclear factor, activated transcription; signal transducer and activator of transcription; suberanilohydroxamic acid; transcription factor; transcription factor binding site