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bioRxiv · 10.1101/096511

Histone H3K4 and H3K36 methylation promotes recruitment, but not activity, of the NuA3 histone acetyltransferase complex in S. cerevisiae

Martin, B. J.·McBurney, K. L.·Maltby, V. E.·Jensen, K. N.·Brind Amour, J.·Howe, L. J.
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Abstract

Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatin-modifying complexes with nucleosomes. The majority of chromatin-modifying complexes contain multiple domains that preferentially interact with modified histones, leading to speculation that these domains function in concert to target nucleosomes with distinct combinations of histone PTMs. In S. cerevisiae, the NuA3 histone acetyltransferase complex contains three domains, the PHD finger in Yng1, the PWWP domain in Pdp3, and the YEATS domain in Taf14, which in vitro bind to H3K4 methylation, H3K36 methylation, and acetylated and crotonylated H3K9 respectively. However the relative in vivo contributions of these histone PTMs in targeting NuA3 is unknown. Here we show that in vivo H4K4 and H3K36 methylation, but not acetylated or crotonylated H3K9, recruit NuA3 to transcribed genes. Through genome-wide colocalization and by mutational interrogation, we demonstrate that the PHD finger of Yng1, and the PWWP domain of Pdp3 independently target NuA3 to H3K4 and H3K36 methylated chromatin respectively. In contrast, we find no evidence to support the YEATS domain of Taf14 functioning in NuA3 recruitment. Collectively our results suggest that the presence of multiple histone-PTM binding domains within NuA3, rather than restricting it to nucleosomes containing distinct combinations of histone PTMs, can serve to increase the range of nucleosomes bound by the complex. Interestingly however, the simple presence of NuA3 is insufficient to ensure acetylation of the associated nucleosomes, suggesting a secondary level of acetylation regulation that does not involve control of HAT-nucleosome interactions

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Martin, B. J., McBurney, K. L., Maltby, V. E., Jensen, K. N., Brind Amour, J., Howe, L. J.. 2016-12-23. Histone H3K4 and H3K36 methylation promotes recruitment, but not activity, of the NuA3 histone acetyltransferase complex in S. cerevisiae. https://doi.org/10.1101/096511

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