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PMID: 18396160 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Intracellular delivery of acetyl-histone peptides inhibits native bromodomain-chromatin interactions and impairs mitotic progression.

FEBS letters ·Vol. 582 ·No. 10 ·2008-04-30 ·Pages 1501-7

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

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.

MeSH Terms
Acetylation Amino Acid Sequence Animals Chromatin/drug effects,metabolism Histones/chemistry,metabolism,pharmacology Mice Mitosis/drug effects Molecular Sequence Data NIH 3T3 Cells Nuclear Proteins/antagonists & inhibitors,genetics,metabolism Peptides/chemistry,metabolism,pharmacology Protein Structure, Tertiary RNA, Small Interfering/genetics Transcription Factors/antagonists & inhibitors,genetics,metabolism tat Gene Products, Human Immunodeficiency Virus/chemistry
Chemicals
Brd4 protein, mouse Chromatin Histones Nuclear Proteins Peptides RNA, Small Interfering Transcription Factors tat Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nishiyama Akira
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.
Mochizuki Kazuki
Mueller Florian
Karpova Tatiana
McNally James G
Ozato Keiko
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Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
0014-5793
DOI
10.1016/j.febslet.2008.03.044
Published
2008-04-30
Epub
2008-00-07
Pages
1501-7
Language
English
Region
England
NLM ID
0155157
PMCID
PMC4120274
Subset
IM
Grants
Intramural NIH HHS · Z01 HD008815-01 · United States
Intramural NIH HHS · Z99 HD999999 · United States
External Links
PubMed source DOI: 10.1016/j.febslet.2008.03.044 PMC Full Text View journal details
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