Article

The transcriptional coactivator MAML1 regulates p300 autoacetylation and HAT activity

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Nucleic Acids Research (Impact Factor: 9.11). 04/2009; 37(9):2996-3006. DOI: 10.1093/nar/gkp163
Source: PubMed

ABSTRACT MAML1 is a transcriptional coregulator originally identified as a Notch coactivator. MAML1 is also reported to interact with other coregulator proteins, such as CDK8 and p300, to modulate the activity of Notch. We, and others, previously showed that MAML1 recruits p300 to Notch-regulated genes through direct interactions with the DNA-CSL-Notch complex and p300. MAML1 interacts with the C/H3 domain of p300, and the p300-MAML1 complex specifically acetylates lysines of histone H3 and H4 tails in chromatin in vitro. In this report, we show that MAML1 potentiates p300 autoacetylation and p300 transcriptional activation. MAML1 directly enhances p300 HAT activity, and this coincides with the translocation of MAML1, p300 and acetylated histones to nuclear bodies.

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Available from: Beverley Marie Dancy, Aug 15, 2014
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    • "EGR1 alone activated the p300-luc reporter in the presence of TPA, and co-transfection of MAML1 with EGR1 strongly increased the activity of the p300 reporter (Figure 3A). We hypothesized that MAML1 may regulate the expression of p300, as well as the acetylation activity of p300 [11]. Lysates were prepared from a FLAG-MAML1 cell line and HEK-293 control cells, and the levels of p300 were analyzed by Western blotting using an antibody recognizing p300. "
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    PLoS ONE 09/2012; 7(9):e46001. DOI:10.1371/journal.pone.0046001 · 3.23 Impact Factor
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    • "Thus, we concluded that SIRT1 deacetylase activity altered the endothelial Notch signaling cascade by deacetylating N1IC and antagonizing p300. Hansson et al. showed that MAML1 (Notch coactivator) could potentiate p300 autoacetylation and p300 transcriptional activation [19]. However, our results suggest that SIRT1 physically interacts with and represses p300 transactivation in an NAD-dependent manner. "
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    PLoS ONE 09/2012; 7(9):e45331. DOI:10.1371/journal.pone.0045331 · 3.23 Impact Factor
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    • "Instead, we used a mouse strain that expresses a dominant negative form of Master-mind-like (DN-MAML) under the control of the ROSA26 locus after hGFAP-driven-Cre-induced recombination. MAML proteins bind the NICD/RBP-J complex and act as scaffolds to recruit coactivators, such as p300 (Fryer et al., 2002; Hansson et al., 2009). The DN-MAML lacks its activation domain to recruit transcriptional coactivators and blocks Notch signaling from all four Notch receptors (Tu et al., 2005). "
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