Higher order chromatin structures are taking shape

Schalch, Thomas

doi:10.1016/j.zemedi.2017.03.002

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…Recent advances have shown that at the kilo- to megabase scale, the chromatin fiber organizes into preferentially interacting regions, referred to as Chromosomally Interacting Domains (CIDs) or Topologically Associating Domains (TADs), which for example regulate enhancer–promoter interactions and replication units through the action of cohesin and CTCF [12,13]. TADs further associate with other domains of similar properties into compartments of heterochromatin and euchromatin [14,15]. At the chromosomal level, chromosomes occupy non-overlapping territories in interphase, and compact to their highest degree as metaphase chromosomes during mitosis [16,17].…”

Section: Introductionmentioning

confidence: 99%

Chromatin fiber structural motifs as regulatory hubs of genome function?

Moraru

Schalch

2019

Essays in Biochemistry

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Nucleosomes cover eukaryotic genomes like beads on a string and play a central role in regulating genome function. Isolated strings of nucleosomes have the potential to compact and form higher order chromatin structures, such as the well-characterized 30-nm fiber. However, despite tremendous advances in observing chromatin fibers in situ it has not been possible to confirm that regularly ordered fibers represent a prevalent structural level in the folding of chromosomes. Instead, it appears that folding at a larger scale than the nucleosome involves a variety of random structures with fractal characteristics. Nevertheless, recent progress provides evidence for the existence of structural motifs in chromatin fibers, potentially localized to strategic sites in the genome. Here we review the current understanding of chromatin fiber folding and the emerging roles that oligonucleosomal motifs play in the regulation of genome function.

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Section: Introductionmentioning

confidence: 99%

Chromatin fiber structural motifs as regulatory hubs of genome function?

Moraru

Schalch

2019

Essays in Biochemistry

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“…Eukaryotic genomes are highly organized and division into euchromatic and heterochromatic compartments is crucial for the correct execution of gene expression programs, for establishment of chromosomal structures such as telomeres and centromeres and for protection of the genome from parasitic genetic elements (Grewal and Jia 2007;Schalch 2017).…”

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Transcriptional gene silencing requires dedicated interaction between HP1 protein Chp2 and chromatin remodeler Mit1

2019

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Heterochromatin protein 1 (HP1) proteins are key factors of eukaryotic heterochromatin that coordinate chromatin compaction and transcriptional gene silencing. Through their multivalency they act as adaptors between histone H3 Lys9 di/trimethyl marks in chromatin and effector complexes that bind to the HP1 chromoshadow domain. Most organisms encode for multiple HP1 isoforms and the molecular mechanisms that underpin their diverse functions in genome regulation remain poorly understood. In fission yeast, the two HP1 proteins Chp2 and Swi6 assume distinct roles and Chp2 is tightly associated with the nucleosome remodeling and deacetylation complex SHREC. Here we show that Chp2 directly engages the SHREC nucleosome remodeler subunit Mit1. The crystal structure of the interaction interface reveals an extraordinarily extensive and specific interaction between the chromoshadow domain of Chp2 and the N terminus of Mit1. The integrity of this interface is critical for high affinity binding and for heterochromatin formation. Comparison with Swi6 shows that the Chp2-Mit1 interface is highly selective and thereby provides the molecular basis for the functional specialization of an HP1 isoform.

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The probabilities of one- and multi-track events for modeling radiation-induced cell kill

Schneider

Vasi

Besserer

2017

Radiat Environ Biophys

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In view of the clinical importance of hypofractionated radiotherapy, track models which are based on multi-hit events are currently reinvestigated. These models are often criticized, because it is believed that the probability of multi-track hits is negligible. In this work, the probabilities for one- and multi-track events are determined for different biological targets. The obtained probabilities can be used with nano-dosimetric cluster size distributions to obtain the parameters of track models. We quantitatively determined the probabilities for one- and multi-track events for 100, 500 and 1000 keV electrons, respectively. It is assumed that the single tracks are statistically independent and follow a Poisson distribution. Three different biological targets were investigated: (1) a DNA strand (2 nm scale); (2) two adjacent chromatin fibers (60 nm); and (3) fiber loops (300 nm). It was shown that the probabilities for one- and multi-track events are increasing with energy, size of the sensitive target structure, and dose. For a 2 × 2 × 2 nm target, one-track events are around 10,000 times more frequent than multi-track events. If the size of the sensitive structure is increased to 100-300 nm, the probabilities for one- and multi-track events are of the same order of magnitude. It was shown that target theories can play a role for describing radiation-induced cell death if the targets are of the size of two adjacent chromatin fibers or fiber loops. The obtained probabilities can be used together with the nano-dosimetric cluster size distributions to determine model parameters for target theories.

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Higher order chromatin structures are taking shape

Abstract: ForumHigher order chromatin structures are taking shape Chromatinstrukturen höherer Ordnung nehmen Gestalt an.

Cited by 3 publications

References 26 publications

Chromatin fiber structural motifs as regulatory hubs of genome function?

Chromatin fiber structural motifs as regulatory hubs of genome function?

Transcriptional gene silencing requires dedicated interaction between HP1 protein Chp2 and chromatin remodeler Mit1

The probabilities of one- and multi-track events for modeling radiation-induced cell kill

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