TY - JOUR
T1 - Structural Basis of Site-Specific Histone Recognition by the Bromodomains of Human Coactivators PCAF and CBP/p300
AU - Zeng, Lei
AU - Zhang, Qiang
AU - Gerona-Navarro, Guillermo
AU - Moshkina, Natalia
AU - Zhou, Ming Ming
N1 - Funding Information:
We thank S. Yan for technical support of the initial protein preparation. M.-M.Z. is supported by funds from the Dr. Golden and Harold Lamport Chair, the National Institutional Institutes, and National Science Foundation, and acknowledges generous access to the New York Structural Biology Center's NMR facilities.
PY - 2008/4/8
Y1 - 2008/4/8
N2 - Histone lysine acetylation is central to epigenetic control of gene transcription. Bromodomains of chromosomal proteins function as acetyl-lysine (Kac) binding domains. However, how bromodomains recognize site-specific histones remains unanswered. Here, we report three three-dimensional solution structures of the bromodomains of the human transcriptional coactivators CREB-binding protein (CBP) and p300/CBP-associated factor (PCAF) bound to peptides derived from histone acetylation sites at lysines 36 and 9 in H3, and lysine 20 in H4. From structural and biochemical binding analyses, we determine consensus histone recognition by the bromodomains of PCAF and CBP, which represent two different subgroups of the bromodomain family. Through bromodomain residues in the ZA and BC loops, PCAF prefers acetylation sites with a hydrophobic residue at (Kac+2) position and a positively charged or aromatic residue at (Kac+3), whereas CBP favors bulky hydrophobic residues at (Kac+1) and (Kac+2), a positively charged residue at (Kac-1), and an aromatic residue at (Kac-2).
AB - Histone lysine acetylation is central to epigenetic control of gene transcription. Bromodomains of chromosomal proteins function as acetyl-lysine (Kac) binding domains. However, how bromodomains recognize site-specific histones remains unanswered. Here, we report three three-dimensional solution structures of the bromodomains of the human transcriptional coactivators CREB-binding protein (CBP) and p300/CBP-associated factor (PCAF) bound to peptides derived from histone acetylation sites at lysines 36 and 9 in H3, and lysine 20 in H4. From structural and biochemical binding analyses, we determine consensus histone recognition by the bromodomains of PCAF and CBP, which represent two different subgroups of the bromodomain family. Through bromodomain residues in the ZA and BC loops, PCAF prefers acetylation sites with a hydrophobic residue at (Kac+2) position and a positively charged or aromatic residue at (Kac+3), whereas CBP favors bulky hydrophobic residues at (Kac+1) and (Kac+2), a positively charged residue at (Kac-1), and an aromatic residue at (Kac-2).
KW - DNA
KW - PROTEINS
UR - http://www.scopus.com/inward/record.url?scp=41449114497&partnerID=8YFLogxK
U2 - 10.1016/j.str.2008.01.010
DO - 10.1016/j.str.2008.01.010
M3 - Article
C2 - 18400184
AN - SCOPUS:41449114497
SN - 0969-2126
VL - 16
SP - 643
EP - 652
JO - Structure
JF - Structure
IS - 4
ER -