title: Intracellular delivery of acetyl-histone peptides inhibits native bromodomain-chromatin interactions and impairs mitotic progression.
abstract: Bromodomains present in Brd4 and other chromatin proteins interact with acetylated histones to regulate transcription and cell growth. To study Brd4-chromatin interactions in vivo, histone H4 tail peptides were fused to a synthetic protein transduction domain (PTD) derived from the human immunodeficiency virus Tat and delivered into cultured cells. Acetyl-H4 peptides, but not unacetylated H4 peptides inhibited real time Brd4-chromatin interactions in living cells as assessed by fluorescence recovery after photobleaching assays. The acetyl-H4 peptides also inhibited an interaction of Brd4 with chromosomes during mitosis and reduced cell growth potential. Together, PTD-based delivery of histone tail peptides offers a novel means to study the mechanism and biological significance of bromodomain-chromatin interactions in vivo.
authors.affiliation: Laboratory of Molecular Growth Regulation, Genomics and Differentiation Program, National Institutes of Child Health and Human Development, National Institutes of Health, Building 6, Room 2A01, 6 Center Drive, Bethesda, MD 20892-2753, United States.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Kazuki
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Florian
authors.initials: F
authors.lastname: Mueller
authors.forename: Tatiana
authors.initials: T
authors.lastname: Karpova
authors.forename: James G
authors.initials: JG
authors.lastname: McNally
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry; D000092468:Bromodomain Containing Proteins
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D010455:Peptides; D034741:RNA, Small Interfering; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; C486694:Brd4 protein, mouse; D000092468:Bromodomain Containing Proteins