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Intracellular delivery of acetyl‐histone peptides inhibits native bromodomain–chromatin interactions and impairs mitotic progression
Author(s) -
Nishiyama Akira,
Mochizuki Kazuki,
Mueller Florian,
Karpova Tatiana,
McNally James G.,
Ozato Keiko
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.03.044
Subject(s) - bromodomain , chromatin , histone , microbiology and biotechnology , histone h4 , biology , brd4 , mitosis , chromatin remodeling , acetylation , histone modifying enzymes , biochemistry , chemistry , dna , gene
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.