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Shaping the cellular landscape with Set2/SETD2 methylation

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Abstract

Chromatin structure is a major barrier to gene transcription that must be disrupted and re-set during each round of transcription. Central to this process is the Set2/SETD2 methyltransferase that mediates co-transcriptional methylation to histone H3 at lysine 36 (H3K36me). Studies reveal that H3K36me not only prevents inappropriate transcriptional initiation from arising within gene bodies, but that it has other conserved functions that include the repair of damaged DNA and regulation of pre-mRNA splicing. Consistent with the importance of Set2/SETD2 in chromatin biology, mutations of SETD2, or mutations at or near H3K36 in H3.3, have recently been found to underlie cancer development. This review will summarize the latest insights into the functions of Set2/SETD2 in genome regulation and cancer development.

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Acknowledgements

We thank Deepak Jha, Howard Fried, and Julia DiFiore for helpful comments and suggestions. The work in the Strahl lab is supported by NIH grants GM110058 and GM68088 to BDS.

Authors’ contributions

SLM and BDS conceived, drafted, and wrote the manuscript.

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  1. Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, 53706, USA

    Stephen L. McDaniel

  2. Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, 27599, USA

    Brian D. Strahl

  3. Department of Biochemistry, University of North Carolina, Chapel Hill, NC, 27599, USA

    Brian D. Strahl

  4. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA

    Brian D. Strahl

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McDaniel, S.L., Strahl, B.D. Shaping the cellular landscape with Set2/SETD2 methylation. Cell. Mol. Life Sci. 74, 3317–3334 (2017). https://doi.org/10.1007/s00018-017-2517-x

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