title: The tumor suppressor inhibitor of growth 4 binds double-stranded DNA through its disordered central region.
abstract: The tumor suppressor inhibitor of growth 4 (ING4) regulates chromatin structure by recruiting the histone acetyl transferase complex HBO1 to sites with histone H3 trimethylated at K4. ING4 dimerizes through its N-terminal domain and recognizes H3K4me3 by the C-terminal plant homeodomain (PHD). The central region of ING4 is disordered and contains the nuclear localization signal. Here, utilizing electrophoresis and nuclear magnetic resonance, we show that ING4 binds double-stranded DNA through its central region with micromolar affinity. Our findings suggest that the cooperativity arising from the presence of two DNA-binding regions in the ING4 dimer, as well as two H3K4me3-binding PHD fingers, may strengthen nucleosome binding and HBO1 complex recruitment.
authors.affiliation: CIC bioGUNE, Derio, Spain.
authors.forename: Georgina
authors.initials: G
authors.lastname: Ormaza
authors.affiliation: Elettra Sincrotrone Trieste, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Medagli
authors.affiliation: CIC bioGUNE, Derio, Spain.
authors.forename: Alain
authors.initials: A
authors.lastname: Ibáñez de Opakua
authors.affiliation: CIC bioGUNE, Derio, Spain.
authors.forename: Jhon A
authors.initials: JA
authors.lastname: Rodríguez
authors.affiliation: CIC bioGUNE, Derio, Spain.
authors.forename: Nekane
authors.initials: N
authors.lastname: Merino
authors.affiliation: CIC bioGUNE, Derio, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Villate
authors.affiliation: Elettra Sincrotrone Trieste, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Onesti
authors.affiliation: CIC bioGUNE, Derio, Spain.|IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
mesh_terms: D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005453:Fluorescence; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017186:Titrimetry; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D050505:Mutant Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA
keywords: DNA binding; chromatin remodeling; electrophoretic mobility shift assay; inhibitor of growth 4; nuclear magnetic resonance; tumor suppressor