Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation

• John W Edmunds ^[1] ; Louis C Mahadevan ^[1] ; Alison L Clayton ^[1]
  1. [1] Nuclear Signalling Laboratory, Department of Biochemistry, Oxford University, Oxford, UK
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 27, Nº. 2, 2007, págs. 406-420
• Idioma: inglés
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• Resumen

  • Understanding the function of histone modifications across inducible genes in mammalian cells requires quantitative, comparative analysis of their fate during gene activation and identification of enzymes responsible. We produced high-resolution comparative maps of the distribution and dynamics of H3K4me3, H3K36me3, H3K79me2 and H3K9ac across c-fos and c-jun upon gene induction in murine fibroblasts. In unstimulated cells, continuous turnover of H3K9 acetylation occurs on all K4-trimethylated histone H3 tails; distribution of both modifications coincides across promoter and 5′ part of the coding region. In contrast, K36- and K79-methylated H3 tails, which are not dynamically acetylated, are restricted to the coding regions of these genes. Upon stimulation, transcription-dependent increases in H3K4 and H3K36 trimethylation are seen across coding regions, peaking at 5′ and 3′ ends, respectively. Addressing molecular mechanisms involved, we find that Huntingtin-interacting protein HYPB/Setd2 is responsible for virtually all global and transcription-dependent H3K36 trimethylation, but not H3K36-mono- or dimethylation, in these cells. These studies reveal four distinct layers of histone modification across inducible mammalian genes and show that HYPB/Setd2 is responsible for H3K36 trimethylation throughout the mouse nucleus.