Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes

Alabert, Constance; Loos, Carolin; Voelker-Albert, Moritz; Graziano, Simona; Forné, Ignasi; Reverón-Gómez, Nazaret; Schuh, Lea; Hasenauer, Jan; Marr, Carsten; Imhof, Axel; Groth, Anja

doi:10.1016/j.celrep.2019.12.060

Cited by 62 publications

(97 citation statements)

References 63 publications

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“…In the so-called domain model of histone propagation, preexisting methyl marks on K27 and K36 of the histone H3 tail mutually antagonize their respective methylation rates, such that the site of incorporation of new histones determines their ultimate methylation state. This mechanism is thought to enhance the stability of epigenetic states (Alabert et al, 2020). Based on such findings and our data presented here, we expect a highly diversified impact of the cell cycle on the epigenetic landscape.…”

Section: Discussionsupporting

confidence: 77%

Mitotic activity shapes stage-specific histone modification profiles during Xenopus embryogenesis

Pokrovsky

Forné

Straub

et al. 2020

Preprint

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Forming an embryo from a zygote poses an apparent conflict for epigenetic regulation. On one hand, the de novo induction of cell fate identities requires the establishment and subsequent maintenance of epigenetic information to harnish developmental gene expression. On the other hand, the embryo depends on cell proliferation, and every round of DNA replication dilutes preexisting histone modifications by incorporation of new unmodified histones into chromatin. Here we investigated the possible relationship between the propagation of epigenetic information and the developmental cell proliferation during Xenopus embryogenesis. We systemically inhibited cell proliferation during the G1/S-transition in gastrula embryos and followed their development until the tadpole stage. Comparing wild-type and cell cycle-arrested embryos, we show that the inhibition of cell proliferation is principally compatible with embryo survival and cellular differentiation. In parallel, we quantified by mass spectrometry the abundance of a large set of histone modification states, which reflects the developmental maturation of the embryonic epigenome. The arrested embryos developed abnormal stage-specific histone modification profiles, in which transcriptionally repressive histone marks were overrepresented. Embryos released from the cell cycle block during neurulation reverted back towards normality on morphological, molecular and epigenetic levels. These results indicate that replicational dilution of histone marks has a strong impact on developmental chromatin maturation. We propose that this influence is strong enough to control developmental decisions, specifically in cell populations that switch between resting and proliferating states such as stem cells.

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Section: Discussionsupporting

confidence: 77%

Mitotic activity shapes stage-specific histone modification profiles during Xenopus embryogenesis

Pokrovsky

Forné

Straub

et al. 2020

Preprint

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“…H3K36me2 Forms the Boundaries of H3K27me3 Spread in Wild-Type and H3K27me2 in K27M H3K36 methylation has been shown to inhibit the deposition of H3K27 methylation, and H3K27me3 rarely coexists with H3K36me2/3 on the same nucleosomes (Schmitges et al, 2011;Yuan et al, 2011). Considerable insight into the differences in spreading of H3K27 methylation between H3K27M mutant and wild-type cells can be obtained from its interaction with the intermediate K36 methylation level, H3K36me2, which has previously been shown to oppose intergenic propagation of H3K27me2/3 (Alabert et al, 2020;Lu et al, 2016;Stafford et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

H3K27M in Gliomas Causes a One-Step Decrease in H3K27 Methylation and Reduced Spreading within the Constraints of H3K36 Methylation

Harutyunyan

Chen

et al. 2020

Cell Reports

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The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenomics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional effects on the epigenome. Here, we use isogenic glioma H3K27M +/À cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. We describe a ''step down'' effect of H3K27M on the distribution of H3K27 methylation: me3 is reduced to me2, me2 is reduced to me1, whereas H3K36me2/3 delineates the boundaries for the spread of H3K27me marks. We also observe a replacement of H3K27me2/3 silencing by H3K9me3. Using a computational simulation, we explain our observations by reduced effectiveness of PRC2 and constraints imposed on the deposition of H3K27me by antagonistic H3K36 modifications. Our work further elucidates the effects of H3K27M in gliomas as well as the general principles of deposition in H3K27 methylation.

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“…H3K9me3 was in turn established through the addition of a third methyl group to pre-existing H3K9me2 in G 1 /S, and from newly synthesized H3 acquiring 3 methyl groups in G 2 /M. In contrast, H3K27me2 was largely the result of unmodified residues acquiring 2 methyl groups in G 2 /M, while H3K27me3 re-establishment patterns were similar to H3K9me3, but clearly antagonized by the H3K36me3 mark (Zee et al, 2012;Alabert et al, 2020).…”

Section: Post-replicative Re-establishment Of Histone Marks and Chrommentioning

confidence: 96%

Interactions With Histone H3 & Tools to Study Them

Scott

Campos

2020

Front. Cell Dev. Biol.

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Histones are an integral part of chromatin and thereby influence its structure, dynamics, and functions. The effects of histone variants, posttranslational modifications, and binding proteins is therefore of great interest. From the moment that they are deposited on chromatin, nucleosomal histones undergo dynamic changes in function of the cell cycle, and as DNA is transcribed and replicated. In the process, histones are not only modified and bound by various proteins, but also shuffled, evicted, or replaced. Technologies and tools to study such dynamic events continue to evolve and better our understanding of chromatin and of histone proteins proper. Here, we provide an overview of H3.1 and H3.3 histone dynamics throughout the cell cycle, while highlighting some of the tools used to study their protein-protein interactions. We specifically discuss how histones are chaperoned, modified, and bound by various proteins at different stages of the cell cycle. Established and select emerging technologies that furthered (or have a high potential of furthering) our understanding of the dynamic histone-protein interactions are emphasized. This includes experimental tools to investigate spatiotemporal changes on chromatin, the role of histone chaperones, histone posttranslational modifications, and histone-binding effector proteins.

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Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes

Cited by 62 publications

References 63 publications

Mitotic activity shapes stage-specific histone modification profiles during Xenopus embryogenesis

Mitotic activity shapes stage-specific histone modification profiles during Xenopus embryogenesis

H3K27M in Gliomas Causes a One-Step Decrease in H3K27 Methylation and Reduced Spreading within the Constraints of H3K36 Methylation

Interactions With Histone H3 & Tools to Study Them

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