Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei

Cabianca, Daphne S.; Muñoz-Jiménez, Celia; Kalck, Véronique; Gaidatzis, Dimos; Padeken, Jan; Seeber, Andrew; Askjaer, Peter; Gasser, Susan M.

doi:10.1038/s41586-019-1243-y

Cited by 96 publications

(121 citation statements)

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“…Several mechanisms for autosome chromatin organization have been proposed. These mechanisms include the antagonism between H3K36 methyltransferase MES-4 and H3K27 methyltransferase RPC2 that defines active vs. repressed chromatin boundaries [4,34]; small chromatin loops emanating from the 270 nuclear periphery that allow active transcription within heterochromatin domains [28]; and active retention of histone acetylase to euchromatin that prevents heterochromatin relocalization [33]. Our data that extra-TFIIIC sites are highly overrepresented in autosome arms and cluster in cis near the boundaries of H3K9me3-marked regions warrant future investigation of whether TFIIIC proteins participate in chromatin insulation in C. elegans autosomes.…”

Section: Discussion 235mentioning

confidence: 99%

“…While condensins, a highly conserved class of architectural proteins 65[30], define half of TAD boundaries in the X chromosome [19], their contribution to autosomal chromatin organization is unclear [14,31]. Furthermore, CTCF, another conserved architectural protein central to chromosome organizations in vertebrates, is thought to be lost during the C. elegans evolution [32].How chromatin domains and chromatin states in the C. elegans autosomes are demarcated remains an area of active investigation [4,28,33,34]. 70…”

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confidence: 99%

“…How chromatin domains and chromatin states in the C. elegans autosomes are demarcated remains an area of active investigation [4,28,33,34]. 70…”

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confidence: 99%

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Transcription-independent TFIIIC-bound sites cluster near heterochromatin boundaries within lamina-associated domains in C. elegans

Stutzman

Liang

Beilinson

et al. 2019

Preprint

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BACKGROUND: Chromatin organization is central to precise control of gene expression. In vertebrates, the insulator protein CTCF plays a central role in organizing chromatin into topologically associated domains (TADs). In nematode C. elegans, however, a CTCF homolog is absent, and pervasive TAD structures are limited to the dosage-compensated sex chromosome, leaving the 25 principle of C. elegans chromatin organization unclear. Transcription Factor III C (TFIIIC) is a basal transcription factor complex for RNA Polymerase III (Pol III), also implicated in chromatin organization. TFIIIC binding without Pol III co-occupancy, referred to as extra-TFIIIC binding, has been implicated in insulating active and inactive chromatin domains in yeasts, flies, and mammalian cells. Whether extra-TFIIIC sites are present and contribute to chromatin organization in C. elegans remain unknown. 30 RESULTS: We identified, in C. elegans embryos, 504 TFIIIC-bound sites absent of Pol III and TATAbinding protein co-occupancy characteristic of extra-TFIIIC sites. Extra-TFIIIC sites constituted half of all identified TFIIIC binding sites in the genome. Unlike Pol III-associated TFIIIC sites predominantly localized in the sex chromosome, extra-TFIIIC sites were highly over-represented within autosomes. Extra-TFIIIC sites formed dense clusters in cis. The autosomal regions enriched for extra-TFIIIC site 35 clusters presented a high level of heterochromatin-associated histone H3K9 trimethylation (H3K9me3). Furthermore, extra-TFIIIC site clusters were embedded in the lamina-associated domains. Despite the heterochromatin environment of extra-TFIIIC sites, the individual clusters of extra-TFIIIC sites were devoid of and resided near the individual H3K9me3-marked regions. CONCLUSION: Clusters of extra-TFIIIC sites were pervasive near the outer boundaries of H3K9me3-40 marked regions in C. elegans. Given the reported activity of extra-TFIIIC sites in heterochromatin insulation in yeasts, our observation raised the possibility that TFIIIC may also demarcate heterochromatin in C. elegans. 3 BACKGROUND 45 Eukaryotic genomes are organized into domains of various chromatin features including actively transcribed regions, transcription factor-bound regions, and transcriptionally repressed regions [1-4].Demarcation of chromatin domains is central to precise control and memory of gene expression patterns. Several proteins have been proposed to have activity in demarcating chromatin domains by acting as a physical boundary [5,6], generating nucleosome depleted regions [7], mediating long-range 50 chromatin interactions [8,9], or tethering chromatin to the nuclear periphery [10]. Despite intense studies [11][12][13][14][15], how chromatin domains are demarcated remains poorly understood.The genome of nematode Carnorhabditis elegans has served as a model to study chromatin organization [3,[16][17][18]. The highest level of chromatin organization in C. elegans is the chromatin feature that distinguishes between the X chromosome and the autosomes. The X chrom...

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Section: Discussion 235mentioning

confidence: 99%

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confidence: 99%

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Transcription-independent TFIIIC-bound sites cluster near heterochromatin boundaries within lamina-associated domains in C. elegans

Stutzman

Liang

Beilinson

et al. 2019

Preprint

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“…We do not intend to make a judgment about which of these cases (or perhaps a combination of them in a manner reminiscent of Ref. (15)) is most realistic in vivo, only to show that either is sufficient to explain the presence of peripheral heterochromatin.…”

Section: Random Attachmentsmentioning

confidence: 99%

“…al. found that cec-4 and mrg-1 independently regulate attachment of heterochromatin to the nuclear periphery in C. elegans, with the former providing a weak attraction and the latter anchoring heterochromatin to the periphery in an H3K9me3 independent manner (15). However, the full combination of factors that are required for positioning to the nuclear periphery remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Chromosomal condensation leads to a preference for peripheral heterochromatin

MacPherson

Spakowitz

2019

Preprint

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A layer of dense heterochromatin is found at the periphery of the nucleus. Because this peripheral heterochromatin functions as a repressive phase, mechanisms that relocate genes to the periphery play an important role in regulating transcription. Using Monte-Carlo simulations, we show that an interaction between chromatin and the nuclear boundary need not be specific to heterochromatin in order to preferentially locate heterochromatin to the nuclear periphery. This observation considerably broadens the class of possible interactions that result in peripheral positioning to include boundary interactions that either weakly attract all chromatin or strongly bind to a randomly chosen small subset of loci. The key distinguishing feature of heterochromatin is its high chromatin density with respect to euchromatin. In our model this densification is caused by HP1's preferential binding to H3K9me3 marked histone tails. We conclude that factors that are themselves unrelated to the nuclear periphery can determine which genomic regions condense to form heterochromatin and thereby control which regions are relocated to the periphery.

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Analysis of Nuclear Pore Complexes in Caenorhabditis elegans by Live Imaging and Functional Genomics

Ruiz

Romero-Bueno

Askjaer

2022

Methods in Molecular Biology

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Nuclear pore complexes (NPCs) are essential to communication of macromolecules between the cell nucleus and the surrounding cytoplasm. RNA synthesized in the nucleus is exported through NPCs to function in the cytoplasm, whereas transcription factors and other proteins are selectively and actively imported. In addition, many NPC constituents, known as nuclear pore proteins (nucleoporins or nups), also play critical roles in other processes, such as genome organization, gene expression and kinetochore function. Thanks to its genetic amenability and transparent body, the nematode Caenorhabditis elegans is an attractive model to study NPC dynamics. We provide here an overview of available genome engineered strains and FLP/Frt-based tools to study tissue-specific functions of individual nucleoporins. We also present protocols for live imaging of fluorescently tagged nucleoporins in intact tissues of embryos, larvae and adult and for analysis of interactions between nucleoporins and chromatin by DamID.

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Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei

Cited by 96 publications

References 45 publications

Transcription-independent TFIIIC-bound sites cluster near heterochromatin boundaries within lamina-associated domains in C. elegans

Transcription-independent TFIIIC-bound sites cluster near heterochromatin boundaries within lamina-associated domains in C. elegans

Chromosomal condensation leads to a preference for peripheral heterochromatin

Analysis of Nuclear Pore Complexes in Caenorhabditis elegans by Live Imaging and Functional Genomics

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