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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Acetylation
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Amino Acid Sequence
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Animals
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Chromatin / drug effects*
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Chromatin / metabolism
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Histones / chemistry
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Histones / metabolism
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Histones / pharmacology*
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Mice
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Mitosis / drug effects*
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Molecular Sequence Data
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NIH 3T3 Cells
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Peptides / chemistry
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Peptides / metabolism
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Peptides / pharmacology*
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Protein Structure, Tertiary
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RNA, Small Interfering / genetics
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Transcription Factors / antagonists & inhibitors*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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tat Gene Products, Human Immunodeficiency Virus / chemistry
Substances
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Brd4 protein, mouse
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Chromatin
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Histones
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Nuclear Proteins
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Peptides
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RNA, Small Interfering
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Transcription Factors
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tat Gene Products, Human Immunodeficiency Virus