Molecular Architecture of Quartet MOZ/MORF Histone Acetyltransferase Complexes

@article{Ullah2008MolecularAO,
  title={Molecular Architecture of Quartet MOZ/MORF Histone Acetyltransferase Complexes},
  author={M. Ullah and N. Pelletier and L. Xiao and Song Ping Zhao and Kainan Wang and C. Degerny and Soroush Tahmasebi and Christelle Cayrou and Y. Doyon and Siew-Lee Goh and N. Champagne and J. C{\^o}t{\'e} and Xiang-Jiao Yang},
  journal={Molecular and Cellular Biology},
  year={2008},
  volume={28},
  pages={6828 - 6843}
}
ABSTRACT The monocytic leukemia zinc finger protein MOZ and the related factor MORF form tetrameric complexes with ING5 (inhibitor of growth 5), EAF6 (Esa1-associated factor 6 ortholog), and the bromodomain-PHD finger protein BRPF1, -2, or -3. To gain new insights into the structure, function, and regulation of these complexes, we reconstituted them and performed various molecular analyses. We found that BRPF proteins bridge the association of MOZ and MORF with ING5 and EAF6. An N-terminal… Expand
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References

SHOWING 1-10 OF 73 REFERENCES
The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity
TLDR
It is concluded that Brpf1, coordinated by its particular set of domains, acts by multiple mechanisms to mediate Moz-dependent histone acetylation and to mark Hox genes for maintained expression throughout vertebrate development. Expand
Expression, purification, and analysis of MOZ and MORF histone acetyltransferases.
TLDR
These methods are useful not only for functional characterization of MOZ, MORF, PCAF, and other HATs, but also for preparation of HAT proteins to screen compound libraries and obtain inhibitors with potential therapeutic value. Expand
Structural and Functional Conservation of the NuA4 Histone Acetyltransferase Complex from Yeast to Humans
TLDR
The NuA4 HAT complex is highly conserved in eukaryotes, in which it plays primary roles in transcription, cellular response to DNA damage, and cell cycle control. Expand
The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase
TLDR
MOZ is a HAT with characteristics of a transcriptional coregulator, supporting the hypothesis that aberrant acetylation by abnormal MOZ proteins leads to leukemogenesis. Expand
MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2
TLDR
It is described that MOZ and MORF both interact with Runx2 (or Cbfa1), a Runt-domain transcription factor that is known to play important roles in T cell lymphomagenesis and bone development and it is suggested that both acetyltransferases are involved in regulating transcriptional activation mediated by Runx1 and its homologues. Expand
The Epc-N domain: a predicted protein-protein interaction domain found in select chromatin associated proteins
TLDR
The data suggest that the Epc-N domain is a protein-protein interaction module found in chromatin associated proteins and may serve as a direct link between histone acetylation and methylation statuses. Expand
Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2
TLDR
The structure of the mouse ING2 PHD finger in complex with a histone H3 peptide trimethylated at lysine 4 is reported and strong binding of other ING and YNG PHD fingers suggests that the recognition of H3K4me3 histone code is a general feature of the ING/YNG proteins. Expand
The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases.
TLDR
The diverse superfamily of lysine acetyltransferases executes an acetylation program that is important for different cellular processes and perturbation of such a program may cause the development of cancer and other diseases. Expand
Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.
TLDR
Comparisons with the Gcn5/PCAF and Hat1 proteins suggest a unified mechanism of catalysis and histone binding by HAT proteins, whereby a structurally conserved core domain mediates catalysis, and sequence variability within aStructurally related N- and C-terminal scaffold determines substrate specificity. Expand
The crystal structure of the ING5 PHD finger in complex with an H3K4me3 histone peptide
TLDR
Functional data are the first direct evidence supporting the critical role of ING5 in directing the MOZ/MORF and HBO1 complexes to chromatin, which consequently increases the local HAT activity and stimulates chromatin remodeling. Expand
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