Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication

Reverón-Gómez, Nazaret; González-Aguilera, Cristina; Stewart-Morgan, Kathleen R.; Petryk, Nataliya; Flury, Valentin; Graziano, Simona; Johansen, Jens Vilstrup; Jakobsen, Janus Schou; Alabert, Constance; Groth, Anja

doi:10.1016/j.molcel.2018.08.010

Cited by 213 publications

(236 citation statements)

References 73 publications

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“…The latter analysis not only replicated published data on CTCF-mediated looping changes across the cell cycles, but also revealed novel cell cycle dynamics of polycomb-associated interactions with highest contact enrichment around the time of mitosis. We note that these observations are generally consistent with the dilution and slow recovery of the H3K27me3 mark after the replication fork (Alabert et al, 2015;Reverón-Gómez et al, 2018), as well as an antagonistic relationship between cohesinmediated loop extrusion and looping between RING1B target sites, reported previously (Rhodes et al, 2019). These observations also pose a question of whether polycomb-associated interactions persist in metaphase chromosomes -a possibility since components of CBX2-containing PRC1 remain associated with metaphase chromosomes (Zhen et al, 2014).…”

Section: Discussionsupporting

confidence: 86%

“…They are at their weakest during S phase, progressively strengthening during G2 and not reaching their peak until early G1. This is consistent with the cell cycle kinetics of H3K27me3 abundance at polycomb marked sites with H3K27me3 levels lowest during S phase where they are diluted after the replication fork, and levels of H3K27me3 only accumulating slowly through G2 and not peaking again until G1 of the next cell cycle (Reverón-Gómez et al, 2018).…”

Section: Applications Of Pile-upssupporting

confidence: 86%

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Coolpup.py:versatile pile-up analysis of Hi-C data

Flyamer

Illingworth

Bickmore

2019

Preprint

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Motivation:Hi-C is currently the method of choice to investigate the global 3D organisation of the genome. A major limitation of Hi-C is the sequencing depth required to robustly detect loops in the data. A popular approach used to mitigate this issue, even in single-cell Hi-C data, is genome-wide averaging (pilingup) of peaks, or other features, annotated in high-resolution datasets, to measure their prominence in less deeply sequenced data. However current tools do not provide a computationally efficient and versatile implementation of this approach.Results: Here we describe coolpup.py -a versatile tool to perform pile-up analysis on Hi-C data. We demonstrate its utility by replicating previously published findings regarding the role of cohesin and CTCF in 3D genome organization, as well as discovering novel details of Polycomb-driven interactions. We also present a novel variation of the pile-up approach that can aid the in statistical analysis of looping interactions.We anticipate that coolpup.py will aid in Hi-C data analysis by allowing easy to use, versatile and efficient generation of pileups. Availability and implementation:Coolpup.py is cross-platform, open-source and free (MIT licensed) software. Source code is available from https://github.com/Phlya/coolpuppy and it can be installed from the Python Packaging Index.

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Section: Discussionsupporting

confidence: 86%

Section: Applications Of Pile-upssupporting

confidence: 86%

Coolpup.py:versatile pile-up analysis of Hi-C data

Flyamer

Illingworth

Bickmore

2019

Preprint

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“…It is only through our technique that accurately scores for parental nucleosome position prior to DNA replication that the parental histone origin can be determined. Although ChIP-seq and imaging systems in conjunction with synchronization experiments can detect the restoration dynamics of newly synthesized chromatin (Clement et al, 2018;Reveron-Gomez et al, 2018), such genomewide approaches cannot ascertain the original locale of a parental nucleosome. Thus, our findings here can attribute the inheritance of a repressed state to both the local segregation of parental nucleosomes and to the "write and read" modules of the histone methyltransferase that deposit the repressive modification ( Figure 6).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the in vivo re-deposition of parental histones within the general vicinity of their original genomic position has not yet been examined through direct methods, but instead through proteomics, marking of newly replicated DNA and ChIP-sequencing techniques (Zee et al, 2012;Alabert et al, 2014;Clement et al, 2018;Reveron-Gomez et al, 2018). Although, the combination of these approaches provides insights into the "bulk" re-deposition of parental nucleosomes, these studies cannot determine the fidelity of such re-deposition at a given chromatin domain, key to tackling the mechanisms of epigenetic inheritance.…”

Section: Introductionmentioning

confidence: 99%

Active and repressed chromatin domains exhibit distinct nucleosome segregation during DNA replication

Escobar

Oksuz

Descostes

et al. 2018

Preprint

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Chromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. Yet, accessing the localized strategies preserving chromatin domain inheritance, specifically the transfer of parental, preexisting nucleosomes with their associated post-translational modifications (PTMs) during DNA replication is challenging in living cells. We devised an inducible, proximity-dependent labeling system to irreversibly mark replication-dependent H3.1 and H3.2 histone-containing nucleosomes at single desired loci in mouse embryonic stem cells such that their fate after DNA replication could be followed. Strikingly, repressed chromatin domains are preserved through the local re-deposition of parental nucleosomes. In contrast, nucleosomes decorating active chromatin domains do not exhibit such preservation. Notably, altering cell fate leads to an adjustment in the positional inheritance of parental nucleosomes that reflects the corresponding changes in chromatin structure. These findings point to important mechanisms that contribute to parental nucleosome segregation to preserve cellular identity.

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“…heritable information, similarly to the silenced state. Histone modifications associated with active transcription can be transmitted through DNA replication(Alabert et al 2015;Reverón-Gómez et al 2018) and multiple transcription factors can bind to the histone modifications they generate(Jacobson et al 2000;Owen et al 2000).…”

mentioning

confidence: 99%

Epigenetic Memory Independent of Symmetric Histone Inheritance

Saxton

Rine

2019

Preprint

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Heterochromatic gene silencing is an important form of gene regulation that usually requires specific histone modifications. A popular model posits that inheritance of modified histones, especially in the form of H3-H4 tetramers, underlies inheritance of heterochromatin. Because H3-H4 tetramers are randomly distributed between daughter chromatids during DNA replication, rare occurrences of asymmetric tetramer inheritance within a heterochromatic domain would have the potential to destabilize heterochromatin. This model makes a prediction that shorter heterochromatic domains would experience unbalanced tetramer inheritance more frequently, and thereby be less stable. In contrast to this prediction, we found that shortening a heterochromatic domain in Saccharomyces had no impact on the strength of silencing nor its heritability. Additionally, we found that replisome tetramers are inherited, they are reassembled into nucleosomes that are interspersed with nucleosomes containing newly synthesized H3-H4 tetramers (Prior et al. 1980;Jackson 1988; Schlissel & Rine in press). One model for epigenetic inheritance posits that marked parental histones inherited through DNA replication recruit histone modifiers to deposit similar marks on new adjacent nucleosomes, thereby reestablishing the previous local landscape of histone modifications (Hecht et al. 1995;Hoppe et al. 2002;Gaydos et al. 2014). In support of this model, the H3K27 methyltransferase PRC2 binds preferentially to H3K27me3 in vitro (Hansen et al. 2008) and some other modifying enzymes show a similar ability to bind their histone modifications (Zhang et al. 2008;Hecht et al. 1995;Imai et al. 2000). If this model is correct, modified H3-H4 tetramers would constitute heritable units that drive epigenetic memory of chromatin states.Studies have come to different conclusions regarding whether histones can carry epigenetic memory. In S. pombe, localized methylation of H3K9 can silence a reporter gene, and this silenced state is heritable in the presence of the H3K9 methyltransferase Clr4p as long as the demethylase Epe1p is absent (Audergon et al. 2015;Ragunathan et al. 2015). These studies suggest that histone modifications can facilitate epigenetic inheritance, and caution that such a mechanism is normally obscured by H3K9 demethylation activity. Conversely, induced removal of silencer elements from silenced chromatin in S. cerevisiae causes almost all cells to lose 2006). In contrast, one study in A. thaliana found that a chromatin domain containing only three H3K27me3-marked nucleosomes is inherited more frequently than would be predicted if random segregation of tetramers caused loss events (Yang et al. 2017).However, no study to our knowledge has systematically tested this prediction.To test directly whether inheritance of a chromatin state is affected by chromatin-domain size, we focused on the heterochromatin domains at the HMR and HML loci in S. cerevisiae. These loci contain copies of mating-type genes that are silenced by the activity of Sir proteins. Spec...

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Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication

Cited by 213 publications

References 73 publications

Coolpup.py:versatile pile-up analysis of Hi-C data

Coolpup.py:versatile pile-up analysis of Hi-C data

Active and repressed chromatin domains exhibit distinct nucleosome segregation during DNA replication

Epigenetic Memory Independent of Symmetric Histone Inheritance

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