Recycling of modified H2A-H2B provides short-term memory of chromatin states

Flury, Valentin; Reverón-Gómez, Nazaret; Alcaraz, Nicolás; Stewart-Morgan, Kathleen R.; Wenger, Alice; Klose, Robert J.; Groth, Anja

doi:10.1016/j.cell.2023.01.007

Cited by 53 publications

(29 citation statements)

References 82 publications

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“…The transcription dependency of H3.3K36me2 is consistent with the fact that H3K36me2 relies, in part, on SET-2 direct binding to RNAPII phosphorylated on S2 and S5 (Kizer et al, 2005;Sun et al, 2005). To our knowledge, H3K4me3 and H2BK120ub1, are the only other known modifications whose restoration on newly replicated chromatin is driven by transcription (Flury et al, 2023;Reveron-Gomez et al, 2018;Serra-Cardona et al, 2022).…”

Section: Discussionsupporting

confidence: 84%

“…2F). H2A.Z deposition is known to be tightly coupled to transcription (Flury et al, 2023;Giaimo et al, 2019), and the finding that H2A.Z abundance was lower in DRB and TPL treated cells supports a role for transcription in the localisation of H2A.Z on replicated DNA. On the other hand, H1.X deposition is known to be replication uncoupled but its function remains unclear (Millan-Arino et al, 2016).…”

Section: Rnapii Stabilizes Association Of Many Chromatin Remodelling ...mentioning

confidence: 61%

“…A probable other candidate is H3K36me3, as its writer NSD2 directly bind RNAPII-pS2-S5, and this interaction promotes H3K36me3 deposition on chromatin (Neri et al, 2017;Venkatesh et al, 2012). More recently, H2BK120ub1 has been shown to be coupled with transcription (Flury et al, 2023). Yet, it remains unknown whether transcription is required for the restoration of other histone modifications.…”

Section: Introductionmentioning

confidence: 99%

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Transcription promotes the restoration of chromatin following DNA replication

Bandau

Alvarez

Jiang

et al. 2023

Preprint

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DNA replication results in the transient eviction of nucleosomes, RNAPII and transcription regulators. How chromatin organization is duplicated on the two daughter strands is a central question in epigenetics. In mammals, transcription restarts on newly replicated DNA within a couple of hours, promoting chromatin accessibility. However, the role of transcription in the restoration of other chromatin determinants following DNA replication remains unclear. Here we have monitored protein re-association to newly replicated DNA upon inhibition of transcription using iPOND coupled to quantitative mass spectrometry. We show that nucleosome assembly and the re-establishment of most histone modifications are uncoupled from transcription restart. However, upon transcription inhibition, the re-association of many proteins was altered, including ATP-dependent remodellers, transcription regulators, the histone variant H2A.Z, histone modifiers as well as the restoration of H3.3K36me2. Finally, transcription also provoked the recruitment of several DNA repair proteins, revealing that transcription promotes chromatin reestablishment post-replication but is also a potential source of genotoxic stress.

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Section: Discussionsupporting

confidence: 84%

Section: Rnapii Stabilizes Association Of Many Chromatin Remodelling ...mentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

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Transcription promotes the restoration of chromatin following DNA replication

Bandau

Alvarez

Jiang

et al. 2023

Preprint

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“…As plant cells divide, H3.1 sustains the deposition of H3K27me3 (Jiang & Berger, 2017) thus providing a forward feedback loop to sustain the polycomb repressive state in dividing cells. Recent data in mammalian cells show that the recycling of H2A-H2B after replication provides another positive feedback loop to maintain the patterns of post translational modifications linked to H2A variants and H2B (Flury et al , 2023). Such replication-dependent maintenance mechanisms no longer operate in non-dividing cells, providing opportunities for changing the allocation of chromatin states.…”

Section: Discussionmentioning

confidence: 99%

Histone variants shape chromatin states in Arabidopsis

Jamge

Lorković

Axelsson

et al. 2023

Preprint

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How different intrinsic sequence variation or regulatory modifications of histones regulate nucleosome interactions with transcription remain unclear. To clarify this question, we examine how histone variants and histone modifications assemble in the Arabidopsis thaliana genome, and show that a limited number of chromatin states divide euchromatin and heterochromatin into biologically significant subdomains. We find that histone variants are as significant as histone modifications in determining the composition of chromatin states. Loss of function of the chromatin remodeler DECREASED IN DNA METHYLATION (DDM1) prevents the exchange of the histone variant H2A.Z to H2A.W and impacts the definition and distribution of chromatin states. In the mutant deprived of DDM1 transposons harbor chromatin states normally found only on proteins coding genes in the wild type. We propose that the dynamics of histone variant exchange control the organization of histone modifications into chromatin states, resulting in molecular landmarks that signify whether genes could be transcribed.

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“…These same modifications can then, in turn, modify how TFs read the DNA [42][43][44] . CpG methylation, and some repressive chromatin modifications such as H3K27 trimethylation can also persist through cell division [44][45][46][47][48] to form a memory of past TF activity. Finally, adjacent regulatory elements interact via 3-D looping [49][50][51] , insulation 52 , competition [53][54][55] , and condensate formation 56,57 to regulate the expression of nearby genes.…”

Section: Box 1: Contrasting the Protein And Cis-regulatory Codesmentioning

confidence: 99%

Hold out the genome: A roadmap to solving the cis-regulatory code

Boer

Taipale

2023

Preprint

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Gene expression is regulated by transcription factors that work together to read cis-regulatory DNA sequences. The “cis-regulatory code” - the rules that cells use to determine when, where, and how much genes should be expressed - has proven to be exceedingly complex, but recent advances in the scale and resolution of functional genomics assays and Machine Learning have enabled significant progress towards deciphering this code. However, we will likely never solve the cis-regulatory code if we restrict ourselves to models trained only on genomic sequences; regions of homology can easily lead to overestimation of predictive performance, and there is insufficient sequence diversity in our genomes to learn all relevant parameters. Fortunately, randomly synthesized DNA sequences enable us to test a far larger sequence space than exists in our genomes in each experiment, and designed DNA sequences enable a targeted query of the sequence space to maximally improve the models. Since cells use the same biochemical principles to interpret DNA regardless of its source, models that are trained on these synthetic data can predict genomic activity, often better than genome-trained models. Here, we provide an outlook on the field, and propose a roadmap towards solving the cis-regulatory code by training models exclusively on non-genomic DNA sequences, and using genomic sequences solely for evaluating the resulting models.

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Recycling of modified H2A-H2B provides short-term memory of chromatin states

Cited by 53 publications

References 82 publications

Transcription promotes the restoration of chromatin following DNA replication

Transcription promotes the restoration of chromatin following DNA replication

Histone variants shape chromatin states in Arabidopsis

Hold out the genome: A roadmap to solving the cis-regulatory code

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