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bioRxiv · 10.1101/2021.02.26.432832

H3K36 methylation and DNA-binding are critical for Ioc4 recruitment and Isw1b remodeller function

Li, J.·Bergmann, L.·Webb, K. M.·Gogol, M. M.·Voigt, P.·Liu, Y.·Liang, H.·Smolle, M. M.
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Abstract

The Isw1b chromatin-remodelling complex is specifically recruited to gene bodies to help retain pre-existing histones during transcription by RNA polymerase II. Recruitment is dependent on H3K36 methylation and the Isw1b subunit Ioc4, which contains an N-terminal PWWP domain. Here, we present the crystal structure of the Ioc4-PWWP domain, including a detailed functional characterization of the domain on its own as well as in the context of full-length Ioc4 and the Isw1b remodeller. The Ioc4-PWWP domain preferentially binds H3K36me3-containing nucleosomes. Its ability to bind DNA is required for nucleosome binding. It is also furthered by the unique insertion motif present in Ioc4-PWWP. The ability to bind H3K36me3 and DNA promote the interaction of full-length Ioc4 with nucleosomes in vitro and they are necessary for its recruitment to gene bodies in vivo. Furthermore, a fully functional Ioc4-PWWP domain promotes efficient remodelling by Isw1b and the maintenance of ordered chromatin in vivo, thereby preventing the production of non-coding RNAs.

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Li, J., Bergmann, L., Webb, K. M., Gogol, M. M., Voigt, P., Liu, Y., Liang, H., Smolle, M. M.. 2021-02-26. H3K36 methylation and DNA-binding are critical for Ioc4 recruitment and Isw1b remodeller function. https://doi.org/10.1101/2021.02.26.432832

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