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Two Mammalian MOF Complexes Regulate Transcription Activation by Distinct Mechanisms
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SUMMARY In mammals, MYST family histone acetyltransferase MOF plays important roles in transcription activation by acetylating histone H4 on K16, a prevalent mark associated with chromatin decondensation, and transcription factor p53 on K120, which is important for activation of pro-apoptotic genes. However, little is known about MOF regulation in higher eukaryotes. Here, we report that the acetyltransferase activity of MOF is tightly regulated in two different but evolutionarily conserved complexes, MSL and MOF-MSL1v1. Importantly, we demonstrate that while the two MOF complexes have indistinguishable activity on histone H4 K16, they differ dramatically in acetylating non-histone substrate p53. We further demonstrate that MOF-MSL1v1 is specifically required for optimal transcription activation of p53 target genes both in vitro and in vivo. Our results support a model that these two MOF complexes regulate distinct stages of transcription activation in cooperation with other histone modifying activities.
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Cites
High-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845
Acetylation of the p53 DNA-binding domain regulates apoptosis induction.
Sykes, S. M., Mellert, H. S., Holbert, M. A., Li, K., Marmorstein, R., Lane, W. S., & McMahon, S. B. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.026 · Cited by 752
Cited by
Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence
Li, T., Kon, N., Jiang, L., Tan, M., Ludwig, T., Zhao, Y., Baer, R., & Gu, W. (2012) · Cell · doi:10.1016/j.cell.2012.04.026 · Cited by 912
p53 modifications: exquisite decorations of the powerful guardian
Liu, Y., Tavana, O., & Gu, W. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz060 · Cited by 392
A novel Alzheimer disease locus located near the gene encoding tau protein
Jun, G., Ibrahim-Verbaas, C. A., Vronskaya, M., Lambert, J.-C., Chung, J., Naj, A. C., Kunkle, B. W., Wang, L.-S., Bis, J. C., Bellenguez, C., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.23 · Cited by 297
Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome
Koolen, D. A., Kramer, J. M., Neveling, K., Nillesen, W. M., Moore-Barton, H. L., Elmslie, F. V., Toutain, A., Amiel, J., Malan, V., Tsai, A. C.-H., et al. (2012) · Nature Genetics · doi:10.1038/ng.2262 · Cited by 232
Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
Xia, Z., Kon, N., Gu, A. P., Tavana, O., & Gu, W. (2022) · Oncogene · doi:10.1038/s41388-022-02331-9 · Cited by 60
Metadata
- Authors
- Li, X., Wu, L., Corsa, C. A. S., Kunkel, S., & Dou, Y.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 36
- Issue
- 2
- Pages
- 290-301
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1980726773
- Cited by
- 176
- References
- 2
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Li, X., Wu, L., Corsa, C. A. S., Kunkel, S., & Dou, Y. (2009). Two Mammalian MOF Complexes Regulate Transcription Activation by Distinct Mechanisms. Molecular Cell. https://doi.org/10.1016/j.molcel.2009.07.031
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