Selective recognition of acetylated histones by bromodomain proteins visualized in living cells.
Acetylation and other modifications on histones comprise histone codes that govern transcriptional regulatory processes in chromatin. Yet little is known how different histone codes are translated and put into action. Using fluorescence resonance energy transfer, we show that bromodomain-containing proteins recognize different patterns of acetylated histones in intact nuclei of living cells. The bromodomain protein Brd2 selectively interacted with acetylated lysine 12 on histone H4, whereas TAF(II)250 and PCAF recognized H3 and other acetylated histones, indicating fine specificity of histone recognition by different bromodomains. This hierarchy of interactions was also seen in direct peptide binding assays. Interaction with acetylated histone was essential for Brd2 to amplify transcription. Moreover association of Brd2, but not other bromodomain proteins, with acetylated chromatin persisted on chromosomes during mitosis. Thus the recognition of histone acetylation code by bromodomains is selective, is involved in transcription, and potentially conveys transcriptional memory across cell divisions.
Kanno
Tomohiko
T
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Kanno
Yuka
Y
Siegel
Richard M
RM
Jang
Moon Kyoo
MK
Lenardo
Michael J
MJ
Ozato
Keiko
K
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008938:Mitosis; D041681:NIH 3T3 Cells; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic
D006657:Histones; D011993:Recombinant Fusion Proteins