Human gene organization driven by the coordination of replication and transcription

Huvet, Maxime; Nicolay, Samuel; Touchon, Marie; Audit, Benjamin; d’Aubenton-Carafa, Yves; Arnéodo, A.; Thermes, Claude

doi:10.1101/gr.6533407

Cited by 152 publications

(222 citation statements)

References 44 publications

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“…In mammals, gene order conservation has been associated with the regulation of gene expression (Semon and Duret, 2006;Gierman et al, 2007), replication, and chromatin structure (Huvet et al, 2007). Nonrandom patterns of gene expression are found among proximally located rice (Ma et al, 2005) and Arabidopsis (Ren et al, 2007) genes.…”

Section: Distinguishing Features Of the Cerealsmentioning

confidence: 99%

Comparative Genomics of Grasses Promises a Bountiful Harvest

Paterson

Bowers²,

Feltus³

et al. 2009

Plant Physiology

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Section: Distinguishing Features Of the Cerealsmentioning

confidence: 99%

Comparative Genomics of Grasses Promises a Bountiful Harvest

Paterson

Bowers²,

Feltus³

et al. 2009

Plant Physiology

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“…It has been proposed that origins of replication lie frequently between promoters of active genes (MacAlpine and Bell 2005;Huvet et al 2007), which would make transcription and replication fork progression co-oriented ). Furthermore, transcription and replication are thought to be coordinated in the nucleus (Schwaiger and Schü beler 2006;Aladjem 2007) to be spatially and temporally separated.…”

Section: H4k16 Acetylation Links Chromatin With Early Replication Andmentioning

confidence: 99%

Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Schwaiger¹,

Stadler²,

Bell³

et al. 2009

Genes Dev.

146

265

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Duplication of eukaryotic genomes during S phase is coordinated in space and time. In order to identify zones of initiation and cell-type-as well as gender-specific plasticity of DNA replication, we profiled replication timing, histone acetylation, and transcription throughout the Drosophila genome. We observed two waves of replication initiation with many distinct zones firing in early-S phase and multiple, less defined peaks at the end of S phase, suggesting that initiation becomes more promiscuous in late-S phase. A comparison of different cell types revealed widespread plasticity of replication timing on autosomes. Most occur in large regions, but only half coincide with local differences in transcription. In contrast to confined autosomal differences, a global shift in replication timing occurs throughout the single male X chromosome. Unlike in females, the dosage-compensated X chromosome replicates almost exclusively early. This difference occurs at sites that are not transcriptionally hyperactivated, but show increased acetylation of Lys 16 of histone H4 (H4K16ac). This suggests a transcription-independent, yet chromosome-wide process related to chromatin. Importantly, H4K16ac is also enriched at initiation zones as well as early replicating regions on autosomes during S phase. Together, our study reveals novel organizational principles of DNA replication of the Drosophila genome and suggests that H4K16ac is more closely correlated with replication timing than is transcription.[Keywords: Chromatin; Drosophila; microarray; replication] Supplemental material is available at http://www.genesdev.org.

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“…These four main chromatin states were further shown to correlate with MRT, namely from early to late replicating, a transcriptionally active euchromatin state (C1) enriched in insulator binding protein CTCF, a polycomb repressed facultative heterochromatin state (C2), a silent heterochromatin state (C3) not enriched in any available marks and a HP1-associated heterochromatin state (C4). When mapping these chromatin states inside the megabase-sized U-domains Audit et al 2012Audit et al , 2013, where the MRT is U-shaped and its derivative Nshaped like the nucleotide compositional asymmetry in the germline skew N-domains (Brodie of Brodie et al 2005;Touchon et al 2005;Audit et al 2007;Huvet et al 2007;Audit et al 2009;Baker et al 2010;Chen et al 2011;, we have shown that in these replication domains that cover about 50% of the human genome, the replication wave ) proceeds along a directional path through the four chromatin states, from the open euchromatin state C1 at U/N-domain borders successively followed by the three silent chromatin states C2, C3 and C4 at the U/N-domain centers . The complete analysis, of the other half of the genome that is complementary to U-domains ) has confirmed the dichotomic picture proposed in early studies in mouse (Farkash-Amar et al 2008;Hiratani et al 2008Hiratani et al , 2010 and human (Desprat et al 2009;Ryba et al 2010;Yaffe et al 2010) genomes, where early and late replicating regions occur in separated compartments of open and closed chromatin, respectively.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of the human genome: coherence between promoter activity and large-scale chromatin environment

Julienne

Zoufir

Audit

et al. 2013

Frontiers in Life Science

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Increasing knowledge of chromatin structure in various cell types raises the challenge of deciphering the contribution of epigenetic modifications to the regulation of nuclear functions in mammals. In a recent study, we have analysed the genomewide distributions of thirteen epigenetic marks in the human cell line K562 at 100 kb resolution of Mean Replication Timing (MRT) data. Using classical clustering techniques, we have shown that the combinatorial complexity of these epigenetic data can be reduced to four predominant chromatin states that replicate at different periods of the S-phase. C1 is an early replicating transcriptionally active euchromatin state, C2 a mid-S repressive type of chromatin associated with Polycomb complexes, C3 a silent chromatin with lack of chromatin marks that replicates later than C2 but before C4, a HP1-associated heterochromatin state that replicates at the end of S-phase. These four chromatin states display remarkable similarities with those recently reported in fly, worm and plants at higher ∼ 1 kb resolution of gene expression data. Here, we extend our integrative analysis of epigenetic data in the K562 human cell line to this smaller scale by focusing on gene promoters (±3 kb around transcription start sites). We show that these promoters can similarly be classified into four main chromatin states: P1 regroups all the marks of transcriptionally active chromatin and corresponds to CpG rich promoters of highly expressed genes; P2 is notably associated with the histone modification H3K27me3 that is the mark of a polycomb repressed chromatin state; P3 corresponds to promoters that are not enriched for any available marks as the signature of a 'null' or 'black' silent heterochromatin state and P4 characterizes the few gene promoters that contain only the constitutive heterochromatin histone modification H3K9me3. When investigating the coherence between promoter activity (P1, P2, P3 or P4) and the large-scale chromatin environment (C1, C2, C3 or C4), we find that the higher the gene density in a considered 100 kb-window, the higher (resp. the lower) the probability of a P1 active promoter (resp. silent P2, P3 and P4 promoters) to be surrounded by an open euchromatin C1 (resp. facultative C2, black C3 or HP1-associated C4 heterochromatin) environment. From large to small scales, it is mainly C4 and to a lesser extent C3 heterochromatin environments both corresponding to gene poor regions, that strongly conditions promoters to belong to the inactive P3 and P4 classes. If C1 (resp. C2) environment surrounds a majority of corresponding active P1 (resp. P2) promoters, it also contains a non-negligible proportion of inactive P2 and P3 (resp. active P1 and inactive P3) promoters. When further investigating the large-scale organization of human genes with respect to 'master' replication origins that were shown to border megabase-sized U-shaped MRT domains, we reveal some significant enrichment of highly expressed P1 genes in a closed neighbourhood of these early initiation zones consistently...

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Human gene organization driven by the coordination of replication and transcription

Cited by 152 publications

References 44 publications

Comparative Genomics of Grasses Promises a Bountiful Harvest

Comparative Genomics of Grasses Promises a Bountiful Harvest

Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome

Epigenetic regulation of the human genome: coherence between promoter activity and large-scale chromatin environment

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