Two distinct modes for propagation of histone PTMs across the cell cycle

Alabert, Constance; Barth, Teresa K.; Reverón-Gómez, Nazaret; Sidoli, Simone; Schmidt, Andreas; Jensen, Ole N.; Imhof, Axel; Groth, Anja

doi:10.1101/gad.256354.114

Cited by 354 publications

(441 citation statements)

References 41 publications

(73 reference statements)

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“…Although histone PTM inheritance is completed after one cell cycle, important repressive marks like H3K9me3 and H3K27me3 are not fully replenished until the next G 1 phase (9). Groth and co-workers (11) reported an overview of multiple histone PTMs at the replication fork and made very similar observations. However, much remains unclear about how different histone PTMs are transmitted through mitosis.…”

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confidence: 59%

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

Lin

Yuan

Han

et al. 2016

Journal of Biological Chemistry

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How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di-and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/ 2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di-or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2.In eukaryotes, histone proteins facilitate the packaging of DNA molecules. The DNA double helix wraps around histone octamers to form nucleosomes. A histone octamer contains two copies of each core histone H3, H4, H2A, and H2B. A 5th histone, histone H1, is associated with the linker DNA which lies between the nucleosomes. Canonical histone proteins are cell cycle-dependent and are produced in S phase (1, 2), whereas cell cycle-independent histone variants (e.g. H3.3) are synthesized throughout the cell cycle (3). Histone proteins carry numerous post-translational modifications (PTMs) 3 that are involved in multiple functions such as epigenetic regulation of transcription, DNA damage repair, and cell cycle progression (4, 5). To maintain lineage identity and to guide proper transcription, cells must replicate PTMs from old histones onto new histones at each cell division. Major efforts have been devoted to understanding how histones themselves are transmitted through the DNA replication fork in S phase (6). In principle, the newly deposited nucleosomes could contain entirely old or newly synthesized histone proteins, or a mixture of both. Accumulating evidence suggests that most H3/H4 tetramers remain intact, with the exception of some H3.3/H4 tetramers, indicating that nucleosomes should contain either new or ...

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confidence: 59%

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

Lin

Yuan

Han

et al. 2016

Journal of Biological Chemistry

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“…2C, 6G) that makes a significant contribution to the total H3K27me3, unrelated to classical PcG target genes. H3K27me2 is enriched wherever transcriptional activity is low, both in genes and in intergenic regions, but as mass spectrometry/SILAC studies show Alabert et al 2015), it is converted to H3K27me3 at PcG target sites. In transcribed regions, loss of H3K27me2/3 may be caused in part by nucleosome eviction but is, in large part, attributable to the action of the UTX demethylase, which accumulates as a function of transcriptional activity.…”

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confidence: 99%

Genome-wide activities of Polycomb complexes control pervasive transcription

et al. 2015

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Polycomb group (PcG) complexes PRC1 and PRC2 are well known for silencing specific developmental genes. PRC2 is a methyltransferase targeting histone H3K27 and producing H3K27me3, essential for stable silencing. Less well known but quantitatively much more important is the genome-wide role of PRC2 that dimethylates ∼70% of total H3K27. We show that H3K27me2 occurs in inverse proportion to transcriptional activity in most non-PcG target genes and intergenic regions and is governed by opposing roaming activities of PRC2 and complexes containing the H3K27 demethylase UTX. Surprisingly, loss of H3K27me2 results in global transcriptional derepression proportionally greatest in silent or weakly transcribed intergenic and genic regions and accompanied by an increase of H3K27ac and H3K4me1. H3K27me2 therefore sets a threshold that prevents random, unscheduled transcription all over the genome and even limits the activity of highly transcribed genes. PRC1-type complexes also have global roles. Unexpectedly, we find a pervasive distribution of histone H2A ubiquitylated at lysine 118 (H2AK118ub) outside of canonical PcG target regions, dependent on the RING/Sce subunit of PRC1-type complexes. We show, however, that H2AK118ub does not mediate the global PRC2 activity or the global repression and is predominantly produced by a new complex involving L(3)73Ah, a homolog of mammalian PCGF3.

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“…Newly synthesized histones are acetylated on specific H3 and H4 residues but lack position-specific information (Sobel et al 1995;Benson et al 2006;Han et al 2007a;Corpet and Almouzni 2009). Post-replication modification of these histones either occur immediately or occur with extended delays (Alabert et al 2015).…”

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confidence: 99%

Chromatin dynamics during DNA replication

2016

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Chromatin is composed of DNA and histones, which provide a unified platform for regulating DNA-related processes, mostly through their post-translational modification. During DNA replication, histone arrangement is perturbed, first to allow progression of DNA polymerase and then during repackaging of the replicated DNA. To study how DNA replication influences the pattern of histone modification, we followed the cell-cycle dynamics of 10 histone marks in budding yeast. We find that histones deposited on newly replicated DNA are modified at different rates: While some marks appear immediately upon replication (e.g., H4K16ac, H3K4me1), others increase with transcription-dependent delays (e.g., H3K4me3, H3K36me3). Notably, H3K9ac was deposited as a wave preceding the replication fork by ∼5-6 kb. This replication-guided H3K9ac was fully dependent on the acetyltransferase Rtt109, while expression-guided H3K9ac was deposited by Gcn5. Further, topoisomerase depletion intensified H3K9ac in front of the replication fork and in sites where RNA polymerase II was trapped, suggesting supercoiling stresses trigger H3K9 acetylation. Our results assign complementary roles for DNA replication and gene expression in defining the pattern of histone modification.

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Two distinct modes for propagation of histone PTMs across the cell cycle

Cited by 354 publications

References 41 publications

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

Genome-wide activities of Polycomb complexes control pervasive transcription

Chromatin dynamics during DNA replication

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