title: Molecular Models of STAT5A Tetramers Complexed to DNA Predict Relative Genome-Wide Frequencies of the Spacing between the Two Dimer Binding Motifs of the Tetramer Binding Sites.
abstract: STAT proteins bind DNA as dimers and tetramers to control cellular development, differentiation, survival, and expansion. The tetramer binding sites are comprised of two dimer-binding sites repeated in tandem. The genome-wide distribution of the spacings between the dimer binding sites shows a distinctive, non-random pattern. Here, we report on estimating the feasibility of building possible molecular models of STAT5A tetramers bound to a DNA double helix with all possible spacings between the dimer binding sites. We found that the calculated feasibility estimates correlated well with the experimentally measured frequency of tetramer-binding sites. This suggests that the feasibility of forming the tetramer complex was a major factor in the evolution of this DNA sequence variation.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-4264, United States of America.
authors.forename: Bangalore K
authors.initials: BK
authors.lastname: Sathyanarayana
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892-1674, United States of America.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892-1674, United States of America.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Lin
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892-1674, United States of America.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-4264, United States of America.
authors.forename: Byungkook
authors.identifier: http://orcid.org/0000-0002-3339-4582
authors.initials: B
authors.lastname: Lee
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D050799:STAT5 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494093:Stat5a protein, mouse; D025521:Tumor Suppressor Proteins