Dynamics of transcription-dependent H3K36me3 marking by the SETD2:IWS1:SPT6 ternary complex

Abstract

SETD2 contributes to gene expression by marking gene bodies with H3K36me3, which is thought to assist in the concentration of transcription machinery at the small portion of the coding genome. Despite extensive genome-wide data revealing the precise localization of H3K36me3 over gene bodies, the physical basis for the accumulation, maintenance, and sharp borders of H3K36me3 over these sites remains rudimentary. Here we propose a model of H3K36me3 marking based on stochastic transcriptiondependent placement and transcription-independent spreading. Our analysis of the spatial distributions and dynamic features of these marks indicates that transcriptiondependent placement dominates the establishment of H3K36me3 domains compared to transcription-independent spreading processes, and that turnover of H3K36me3 limits its capacity for epigenetic memory. By adding additional terms for asymmetric histone turnover occurring at transcription start sites, our model provides a remarkably accurate representation of H3K36me3 levels and dynamics over gene bodies. Furthermore, we validate our findings by revealing that loss of SPT6 impairs the transcription-coupled activity of the SETD2:IWS1:SPT6 ternary complex, thereby reducing the tight correlation between transcription and H3K36me3 levels at gene bodies.

De novo activated transcription of inserted foreign coding sequences is inheritable in the plant genome

“…Although H2A.Z is a marker histone for the promoter region, it also appears in the gene bodies of genes with low expression [ 45 – 47 ]. In addition, mC and H3K36me3 were reportedly deposited within a gene body in a transcription-coupled manner [ 48 ], which would be undetectable in the low-expressed genes [ 49 ]. Thus, these distribution patterns of chromatin marks in the T2-plants were plausible because the transcriptional strength of these two lines was low compared with that of the constitutive genes (Figs 4C and S2 ).…”

HP1γ regulates H3K36 methylation and pluripotency in embryonic stem cells

“…Despite the fact that HP1γ is known to be a reader of H3K9me3, only 7% of the HP1γ-bound genome (in base pairs) is shared with H3K9me3 (Figure 1D , i , Supplementary Figure S1A ). In contrast, H3K36me3 and H3K79me2, both of which are implicated with transcriptional elongation and are enriched on highly expressed genes ( 22–24 , 50 ), have a greater co-occurrence with HP1γ ( Supplementary Figure S1A ). About 52.6% of HP1γ-bound genome (in base pairs) is shared with H3K36me3, whereas 37% is shared with H3K79me2 (Figure 1D , ii, Supplementary Figure S1A, S1B , i).…”

De novoactivated transcription of inserted foreign coding sequences is inheritable in the plant genome

“…Although H2A.Z is a marker histone for the promoter region, it also appears in the gene bodies of genes with low expression (Lashgari et al, 2017; Gómez-Zambrano, Merini and Calonje, 2019; Lei and Frederic, 2020). In addition, mC and H3K36me3 were reportedly deposited within a gene body in a transcription-coupled manner (Teissandier and Bourc’his, 2017), which would be undetectable in the low-expressed genes (Cermakova et al, 2019). Thus, these distribution patterns of epigenetic marks in the T2-plants were plausible because the transcriptional strength of these two lines was low compared with that of the constitutive genes (Figure 4c, and Figure S2).…”