Transcription organizes euchromatin similar to an active microemulsion

Hilbert, Lennart; Sato, Yuko; Kimurâ, Hiroshi; Jülicher, Frank; Honigmann, Alf; Zaburdaev,; Vastenhouw, Nadine L.

doi:10.1101/234112

Cited by 26 publications

(45 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Тhus, our models indicate that attraction between heterochromatic regions can generate compartmentalization in agreement with Hi-C and global architecture that of inverted nuclei as seen in microscopy. The central role for attractions between heterochromatic regions is in contrast to suggestions from earlier studies concentrated on the role of the lamina 12 and activity-related clustering of euchromatin [13][14][15][16][17] . Importantly, we found that interactions between constitutive heterochromatin ( C , H3K9m3-rich) should be considerably stronger than interactions between facultative heterochromatin ( B , H3K27me3/H4K20me3-rich).…”

contrasting

confidence: 94%

Heterochromatin drives organization of conventional and inverted nuclei

Falk

Feodorova

Naumova

et al. 2018

Preprint

View full text Add to dashboard Cite

The mammalian cell nucleus displays a remarkable spatial segregation of active euchromatic from inactive heterochromatic genomic regions. In conventional nuclei, euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery. In contrast, rod photoreceptors in nocturnal mammals have inverted nuclei, with a dense heterochromatic core and a thin euchromatic outer shell. This inverted architecture likely converts rod nuclei into microlenses to facilitate nocturnal vision, and may relate to the absence of particular proteins that tether heterochromatin to the lamina. However, both the mechanism of inversion and the role of interactions between different types of chromatin and the lamina in nuclear organization remain unknown. To elucidate this mechanism we performed Hi-C and microscopy on cells with inverted nuclei and their conventional counterparts. Strikingly, despite the inversion evident in microscopy, both types of nuclei display similar Hi-C maps. To resolve this paradox we developed a polymer model of chromosomes and found a universal mechanism that reconciles Hi-C and microscopy for both inverted and conventional nuclei. Based solely on attraction between heterochromatic regions, this mechanism is sufficient to drive phase separation of euchromatin and heterochromatin and faithfully reproduces the 3D organization of inverted nuclei. When interactions between heterochromatin and the lamina are added, the same 1 . CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/244038 doi: bioRxiv preprint first posted online Jan. 9, 2018; model recreates the conventional nuclear organization. To further test our models, we eliminated lamina interactions in models of conventional nuclei and found that this triggers a spontaneous process of inversion that qualitatively reproduces the pathway of morphological changes during nuclear inversion in vivo . Together, our experiments and modeling suggest that interactions among heterochromatic regions are central to phase separation of the active and inactive genome in inverted and conventional nuclei, while interactions with the lamina are essential for building the conventional architecture from these segregated phases. Ultimately our data suggest that an inverted organization constitutes the default state of nuclear architecture.Mammalian interphase chromosomes are spatially organized with distinct features ranging from chromosome territories, to active and inactive A/B compartments and to TADs 1,2 . Emerging work argues that these features reflect different underlying mechanisms 3 . Of much recent interest [4][5][6][7][8] , TAD formation appears to result from a cohesin-mediated mechanism of loop extrusion. Compartments are increasingly appreciated as distinct from TADs: compartments both persist when TADs are experimentally disrupted 5,6,8,...

show abstract

contrasting

confidence: 94%

Heterochromatin drives organization of conventional and inverted nuclei

Falk

Feodorova

Naumova

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…We find that the mir-430 cluster, which is transcribed two orders of magnitude higher than any other region, undergoes a dramatic loss in accessibility when elongation of RNA polymerase II is blocked. The miR-430 cluster is one of the first to be transcribed and initially, all transcribing RNA polymerase II localizes to the two alleles of the miR-430 cluster [19][20][21]56], which might facilitate the formation of RNA-pol II 'trains' capable of evicting nucleosomes, as shown in vitro [33].…”

Section: Locusmentioning

confidence: 98%

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Pálfy

Schulze

Valen

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

In many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remains poorly understood. Here, we generated chromatin accessibility maps from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hyper-transcribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription.Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.

show abstract

“…Thus, it is tempting to speculate that chromatin compartments with different transcriptional activity might display different and tunable degrees of "phase separation" , depending on the type, strength, and dynamics of the physical interactions in each compartment (Fig 2). However, biophysical evidence supporting liquid phase separation of transcriptionally active domains remains sparse (Preprint: Hilbert et al, 2017) and their formation might not necessarily involve such separation.…”

Section: Transcription As a Looping Forcementioning

confidence: 99%

Forces driving the three‐dimensional folding of eukaryotic genomes

Rada-Iglesias

Grosveld

Papantonis

2018

Molecular Systems Biology

View full text Add to dashboard Cite

The last decade has radically renewed our understanding of higher order chromatin folding in the eukaryotic nucleus. As a result, most current models are in support of a mostly hierarchical and relatively stable folding of chromosomes dividing chromosomal territories into A‐ (active) and B‐ (inactive) compartments, which are then further partitioned into topologically associating domains (TADs), each of which is made up from multiple loops stabilized mainly by the CTCF and cohesin chromatin‐binding complexes. Nonetheless, the structure‐to‐function relationship of eukaryotic genomes is still not well understood. Here, we focus on recent work highlighting the biophysical and regulatory forces that contribute to the spatial organization of genomes, and we propose that the various conformations that chromatin assumes are not so much the result of a linear hierarchy, but rather of both converging and conflicting dynamic forces that act on it.

show abstract

Transcription organizes euchromatin similar to an active microemulsion

Cited by 26 publications

References 76 publications

Heterochromatin drives organization of conventional and inverted nuclei

Heterochromatin drives organization of conventional and inverted nuclei

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Forces driving the three‐dimensional folding of eukaryotic genomes

Contact Info

Product

Resources

About