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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Nishiyama A,Mochizuki K,Mueller F,Karpova T,McNally JG,Ozato K

doi

10.1016/j.febslet.2008.03.044

subject

Has Abstract

pub_date

2008-04-30 00:00:00

pages

1501-7

issue

10

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(08)00291-3

journal_volume

582

pub_type

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