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Abstract
Human p300 is a transcriptional co-activator and a major acetyltransferase that acetylates histones and other proteins facilitating gene transcription. The activity of p300 relies on the fine-tuned interactome that involves a dozen p300 domains and hundreds of binding partners and links p300 to a wide range of vital signaling events. Here, we report a novel function of the ZZ-type zinc finger (ZZ) of p300 as a reader of histone H3. We show that the ZZ domain and acetyllysine-recognizing bromodomain of p300 play critical roles in modulating p300 enzymatic activity and its association with chromatin. The acetyllysine binding function of bromodomain is essential for acetylation of histones H3 and H4, whereas interaction of the ZZ domain with H3 promotes selective acetylation of the histone H3K27 and H3K18 sites.
Details
; Xue, Yongming 2
; Shi, Jiejun 3
; Ahn, JaeWoo 1 ; Mi, Wenyi 4
; Muzaffar, Ali 1 ; Wang, Xiaolu 4 ; Klein, Brianna J 1 ; Wen, Hong 4 ; Li, Wei 3
; Shi, Xiaobing 5
; Kutateladze, Tatiana G 1
1 Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA
2 Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Genetics and Epigenetics Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA
3 Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
4 Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA
5 Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Genetics and Epigenetics Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA