title: Tumor suppressor genes are larger than apoptosis-effector genes and have more regions of active chromatin: Connection to a stochastic paradigm for sequential gene expression programs.
abstract: Apoptosis- and proliferation-effector genes are substantially regulated by the same transactivators, with E2F-1 and Oct-1 being notable examples. The larger proliferation-effector genes have more binding sites for the transactivators that regulate both sets of genes, and proliferation-effector genes have more regions of active chromatin, i.e, DNase I hypersensitive and histone 3, lysine-4 trimethylation sites. Thus, the size differences between the 2 classes of genes suggest a transcriptional regulation paradigm whereby the accumulation of transcription factors that regulate both sets of genes, merely as an aspect of stochastic behavior, accumulate first on the larger proliferation-effector gene "traps," and then accumulate on the apoptosis effector genes, thereby effecting sequential activation of the 2 different gene sets. As IRF-1 and p53 levels increase, tumor suppressor proteins are first activated, followed by the activation of apoptosis-effector genes, for example during S-phase pausing for DNA repair. Tumor suppressor genes are larger than apoptosis-effector genes and have more IRF-1 and p53 binding sites, thereby likewise suggesting a paradigm for transcription sequencing based on stochastic interactions of transcription factors with different gene classes. In this report, using the ENCODE database, we determined that tumor suppressor genes have a greater number of open chromatin regions and histone 3 lysine-4 trimethylation sites, consistent with the idea that a larger gene size can facilitate earlier transcriptional activation via the inclusion of more transactivator binding sites.
authors.affiliation: a Department of Molecular Medicine ; Morsani College of Medicine; University of South Florida ; Tampa , FL USA.
authors.forename: Marlene
authors.initials: M
authors.lastname: Garcia
authors.forename: James A
authors.initials: JA
authors.lastname: Mauro
authors.forename: Michael
authors.initials: M
authors.lastname: Ramsamooj
authors.forename: George
authors.initials: G
authors.lastname: Blanck
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D027702:Organic Cation Transporter 1 / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D027702:Organic Cation Transporter 1
keywords: apoptosis; bioinformatics; cell cycle arrest; chromatin; gene size; genomics; transcription factors