title: The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis.
abstract: It is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT). However, it is not known whether a specific mitotic factor plays a critical role in reprogramming. Here we identify an isoform of human bromodomain-containing 3 (BRD3), BRD3R (BRD3 with Reprogramming activity), as a reprogramming factor. BRD3R positively regulates mitosis during reprogramming, upregulates a large set of mitotic genes at early stages of reprogramming, and associates with mitotic chromatin. Interestingly, a set of the mitotic genes upregulated by BRD3R constitutes a pluripotent molecular signature. The two BRD3 isoforms display differential binding to acetylated histones. Our results suggest a molecular interpretation for the mitotic advantage in reprogramming and show that mitosis may be a driving force of reprogramming.
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Khodadadi-Jamayran
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Genetics, Howell and Elizabeth Heflin Center for Genomic Science, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Crowley
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Muhamad A
authors.initials: MA
authors.lastname: Festok
authors.affiliation: Department of Genetics, Howell and Elizabeth Heflin Center for Genomic Science, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Crossman
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Townes
authors.affiliation: Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Kejin
authors.initials: K
authors.lastname: Hu
mesh_terms: D000107:Acetylation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D065150:Cellular Reprogramming; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
chemical_list: D006657:Histones; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C109106:BRD3 protein, human; D000092468:Bromodomain Containing Proteins