Poised Transcription Factories Prime Silent uPA Gene Prior to Activation

Ferrai, Carmelo; Xie, Shaoping; Luraghi, Paolo; Munari, Davide; Ramı́rez, Francisco; Branco, Miguel R.; Pombo, Ana; Crippa, Massimo P.

doi:10.1371/journal.pbio.1000270

Cited by 79 publications

(87 citation statements)

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“…In agreement with this, transcription at engineered gene arrays leads to chromatin decompaction (Tsukamoto et al, 2000;Müller et al, 2001). Similarly, gene-rich regions and single genes are localized in regions of decompacted chromatin when they are transcribed (Volpi et al, 2000;Chambeyron and Bickmore, 2004;Ferrai et al, 2010). In addition to affecting the degree of chromatin compaction, transcription has long been suggested to result in DNA-DNA contacts (Cook, 1999).…”

Section: Introductionmentioning

confidence: 91%

Transcription organizes euchromatin similar to an active microemulsion

Hilbert

Sato

Kimurâ

et al. 2017

Preprint

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Graphical abstract HighlightsThe copyright holder for this preprint (which was . http://dx.doi.org/10.1101/234112 doi: bioRxiv preprint first posted online Dec. 15, 2017; Page 2 of 46 SummaryThe three-dimensional organization of the genome is essential for development and health. Although the organization of euchromatin (transcriptionally permissive chromatin) dynamically adjusts to changes in transcription, the underlying mechanisms remain elusive. Here, we studied how transcription organizes euchromatin, using experiments in zebrafish embryonic cells and theory. We show that transcription establishes an interspersed pattern of chromatin domains and RNA-enriched microenvironments. Specifically, accumulation of RNA in the vicinity of transcription sites creates microenvironments that locally remodel chromatin by displacing not transcribed chromatin. Ongoing transcriptional activity stabilizes the interspersed pattern of chromatin domains and RNA-enriched microenvironments by establishing contacts between chromatin and RNA. We explain our observations with an active microemulsion model based on two macromolecular mechanisms: RNA/RNA-binding protein complexes generally segregate from chromatin, while transcribed chromatin is retained among RNA/RNA-binding protein accumulations. We propose that microenvironments might be central to genome architecture and serve as gene regulatory hubs.

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Section: Introductionmentioning

confidence: 91%

Transcription organizes euchromatin similar to an active microemulsion

Hilbert

Sato

Kimurâ

et al. 2017

Preprint

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“…1a). Imaging approaches suggest that active transcription units cluster in sites of transcription, called transcription factories 1,2 , whereas Polycomb-repressed genes are found to associate with Polycomb bodies or poised transcription factories [3][4][5][6] . Genes in the same metabolic pathways can co-localise with each other, especially in specialized cell types, although at low frequency across cell populations 7,8 .…”

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confidence: 99%

“…Although some reports suggest that ES cell chromatin is more dynamic than the chromatin of differentiated cells, with higher exchange of linker histone H1 and nucleosome dynamics 18 , other studies find similar kinetics 19,20,21 . Nevertheless, chromosomes retain their territorial conformation in ES cells, and RNA polymerase II (RNAPII) organizes itself in active and poised transcription factories 3,4,22,23 . Active transcription compartments, or transcription factories 1,8,[24][25][26] , associate with active genes and are characterized by the presence of RNAPII complexes phosphorylated on both Serine5 and Serine2 residues of C-terminal domain of the largest subunit, Rpb1 [2][3][4] .…”

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confidence: 99%

“…Nevertheless, chromosomes retain their territorial conformation in ES cells, and RNA polymerase II (RNAPII) organizes itself in active and poised transcription factories 3,4,22,23 . Active transcription compartments, or transcription factories 1,8,[24][25][26] , associate with active genes and are characterized by the presence of RNAPII complexes phosphorylated on both Serine5 and Serine2 residues of C-terminal domain of the largest subunit, Rpb1 [2][3][4] . Poised transcription factories contain Polycomb and RNAPII phosphorylated on Serine5 only, and co-localise with Polycomb-repressed genes 3,4,27 .…”

mentioning

confidence: 99%

“…Active transcription compartments, or transcription factories 1,8,[24][25][26] , associate with active genes and are characterized by the presence of RNAPII complexes phosphorylated on both Serine5 and Serine2 residues of C-terminal domain of the largest subunit, Rpb1 [2][3][4] . Poised transcription factories contain Polycomb and RNAPII phosphorylated on Serine5 only, and co-localise with Polycomb-repressed genes 3,4,27 . Polycomb repression plays major roles in pluripotent cells through the silencing of early developmental genes, which are kept in a poised state ready for induction in response to signals that commit cells into specific embryonic lineages 5,28,29 .…”

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confidence: 99%

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Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

Barbieri

Xie

Triglia

et al. 2017

Nat Struct Mol Biol

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Gene expression states influence the three-dimensional conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features, which define promoter activation states or CTCF binding sites. Single cell imaging of the locus folding was performed to test model predictions. While CTCF occupancy alone fails to predict the in vivo folding at genomic length scale of 10 kb, we found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fibre fully explain the HoxB folding patterns imaged in single cells. We identify state-dependent promoter interactions as major drivers of chromatin folding in gene-dense regions.The link between gene expression states and long-range chromatin contacts between different transcription units is a major open question in our understanding of gene regulation (Fig. 1a). Imaging approaches suggest that active transcription units cluster in sites of transcription, called transcription factories 1,2 , whereas Polycomb-repressed genes are found to associate with Polycomb bodies or poised transcription factories [3][4][5][6] . Genes in the same metabolic pathways can co-localise with each other, especially in specialized cell types, although at low frequency across cell populations 7,8 . Although the molecular mechanisms that underlie promoter co-associations and their functional purpose remain unclear, they suggest that gene activation states may help to establish cell-type specific chromatin folding configurations that partition active from Polycomb-repressed chromatin domains. CTCF binding has important roles in the formation of chromatin loops and enhancer-promoter interactions [9][10][11][12][13][14] , and has been proposed to organise chromatin domains through loop extrusion mechanisms in gene-poor areas 15 and to help insulate spreading of active marks into Polycomb repressed domains 16 . However, CTCF . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/111773 doi: bioRxiv preprint first posted online Feb. 28, 2017; 3 contribution to the large scale folding of more complex, gene-dense regions remains unknown in particular regions populated with active and Polycomb-repressed loci. residues. Polycomb-repressor complexes can induce chromatin folding independently of catalytic activity [30][31][32] . The co-associations of active genes or Polycomb-repressed genes have so far been studied separately, without assessing whether one type of association might have predominant contributions to chromatin folding at specific loci. Mouse ES cells lack laminTo further understand the und...

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Chromatin Structure and Domains

Grimaud¹

2011

Encyclopedia of Life Sciences

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In the cell nucleus, deoxyribonucleic acid (DNA) is associated with nuclear proteins called histones to form chromatin. According to the type of factors that bind it, chromatin is organised into different subdomains. Chromatin structure is essential to compact DNA but it is also crucial for the proper development of multicellular organisms. Indeed, it is a highly organised structure through which, genetic material is modulated to regulate nuclear processes, including transcription, replication and DNA repair. It is notably regulated via reversible covalent histone modifications. These multiple modifications deposited on chromatin by different histone modifying enzymes, serve as specific recognition signal for DNA‐regulating proteins. More recently, spatial organisation of chromosomes in the nucleus has been identified as a critical feature for chromatin regulation, contributing in the fine tuning of transcription regulation, a major issue of cell differentiation and maintenance of cell identity during development. Key Concepts: Chromatin is a highly structured entity with an important flexibility. The large repertoire of epigenetic modifications offers a wide range of specific molecular and cellular responses. Together with genetic information, epigenetic marks play a critical role in the transmission of gene regulation. Nuclear organisation of chromosomes participates in the inheritance of chromatin states.

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Poised Transcription Factories Prime Silent uPA Gene Prior to Activation

Abstract: The association of poised genes with transcription factories may contribute to rapid transcriptional activation in response to stimuli and to silencing when genes are located at the interior of their chromosome territories.

Cited by 79 publications

References 45 publications

Transcription organizes euchromatin similar to an active microemulsion

Transcription organizes euchromatin similar to an active microemulsion

Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

Chromatin Structure and Domains

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