MYC recruits the TIP60 histone acetyltransferase complex to chromatin.
The transcription factor MYC binds specific DNA sites in cellular chromatin and induces the acetylation of histones H3 and H4. However, the histone acetyltransferases (HATs) that are responsible for these modifications have not yet been identified. MYC associates with TRRAP, a subunit of distinct macromolecular complexes that contain the HATs GCN5/PCAF or TIP60. Although the association of MYC with GCN5 has been shown, its interaction with TIP60 has never been analysed. Here, we show that MYC associates with TIP60 and recruits it to chromatin in vivo with four other components of the TIP60 complex: TRRAP, p400, TIP48 and TIP49. Overexpression of enzymatically inactive TIP60 delays the MYC-induced acetylation of histone H4, and also reduces the level of MYC binding to chromatin. Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.
Frank
Scott R
SR
DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.
Parisi
Tiziana
T
Taubert
Stefan
S
Fernandez
Paula
P
Fuchs
Miriam
M
Chan
Ho-Man
HM
Livingston
David M
DM
Amati
Bruno
B
D000123:Acetyltransferases / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005822:Genetic Vectors; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D011233:Precipitin Tests; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism / Q000502:physiology*; D051381:Rats
D002843:Chromatin; D006657:Histones; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5