Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Irregular Chromatin: Packing Density, Fiber Width, and Occurrence of Heterogeneous Clusters.

ABSTRACT: How chromatin is folded on the length scale of a gene is an open question. Recent experiments have suggested that, in vivo, chromatin is folded in an irregular manner and not as an ordered fiber with a width of 30 nm that is expected from theories of higher order packaging. Using computational methods, we examine how the interplay between DNA-bending nonhistone proteins, histone tails, intrachromatin electrostatic, and other interactions decide the nature of the packaging of chromatin. We show that although the DNA-bending nonhistone proteins make the chromatin irregular, they may not alter the packing density and size of the fiber. We find that the length of the interacting region and intrachromatin electrostatic interactions influence the packing density, clustering of nucleosomes, and the width of the chromatin fiber. Our results suggest that the heterogeneity in the interaction pattern will play an important role in deciding the nature of the packaging of chromatin.

SUBMITTER: Bajpai G

PROVIDER: S-EPMC6950648 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Irregular Chromatin: Packing Density, Fiber Width, and Occurrence of Heterogeneous Clusters.

Bajpai Gaurav G Padinhateeri Ranjith R

Biophysical journal 20191114 1

How chromatin is folded on the length scale of a gene is an open question. Recent experiments have suggested that, in vivo, chromatin is folded in an irregular manner and not as an ordered fiber with a width of 30 nm that is expected from theories of higher order packaging. Using computational methods, we examine how the interplay between DNA-bending nonhistone proteins, histone tails, intrachromatin electrostatic, and other interactions decide the nature of the packaging of chromatin. We show t ...[more]

PMID: 31810656

Similar Datasets

Macrogenomic engineering via modulation of the scaling of chromatin packing density.

Project description:Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in?vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complete cancer cell killing in?vitro. Our findings represent a 'macrogenomic engineering' approach to modulating the physical structure of chromatin for whole-scale transcriptional modulation.

| S-EPMC5809134 | biostudies-literature

An amino acid code for irregular and mixed protein packing.

Project description:To advance our understanding of protein tertiary structure, the development of the knob-socket model is completed in an analysis of the packing in irregular coil and turn secondary structure packing as well as between mixed secondary structure. The knob-socket model simplifies packing based on repeated patterns of two motifs: a three-residue socket for packing within secondary (2°) structure and a four-residue knob-socket for tertiary (3°) packing. For coil and turn secondary structure, knob-sockets allow identification of a correlation between amino acid composition and tertiary arrangements in space. Coil contributes almost as much as ?-helices to tertiary packing. In irregular sockets, Gly, Pro, Asp, and Ser are favored, while in irregular knobs, the preference order is Arg, Asp, Pro, Asn, Thr, Leu, and Gly. Cys, His,Met, and Trp are not favored in either. In mixed packing, the knob amino acid preferences are a function of the socket that they are packing into, whereas the amino acid composition of the sockets does not depend on the secondary structure of the knob. A unique motif of a coil knob with an XYZ ?-sheet socket may potentially function to inhibit ?-sheet extension. In addition, analysis of the preferred crossing angles for strands within a ?-sheet and mixed ?-helice/?-sheet identifies canonical packing patterns useful in protein design. Lastly, the knob-socket model abstracts the complexity of protein tertiary structure into an intuitive packing surface topology map.

| S-EPMC4715706 | biostudies-literature

Disordered chromatin packing regulates phenotypic plasticity.

Project description:Three-dimensional supranucleosomal chromatin packing plays a profound role in modulating gene expression by regulating transcription reactions through mechanisms such as gene accessibility, binding affinities, and molecular diffusion. Here, we use a computational model that integrates disordered chromatin packing (CP) with local macromolecular crowding (MC) to study how physical factors, including chromatin density, the scaling of chromatin packing, and the size of chromatin packing domains, influence gene expression. We computationally and experimentally identify a major role of these physical factors, specifically chromatin packing scaling, in regulating phenotypic plasticity, determining responsiveness to external stressors by influencing both intercellular transcriptional malleability and heterogeneity. Applying CPMC model predictions to transcriptional data from cancer patients, we identify an inverse relationship between patient survival and phenotypic plasticity of tumor cells.

| S-EPMC6949045 | biostudies-literature

G Protein-Coupled Receptors Contain Two Conserved Packing Clusters.

Project description:G protein-coupled receptors (GPCRs) have evolved a seven-transmembrane helix framework that is responsive to a wide range of extracellular signals. An analysis of the interior packing of family A GPCR crystal structures reveals two clusters of highly packed residues that facilitate tight transmembrane helix association. These clusters are centered on amino acid positions 2.47 and 4.53, which are highly conserved as alanine and serine, respectively. Ala2.47 mediates the interaction between helices H1 and H2, while Ser4.53 mediates the interaction between helices H3 and H4. The helical interfaces outside of these clusters are lined with residues that are more loosely packed, a structural feature that facilitates motion of helices H5, H6, and H7, which is required for receptor activation. Mutation of the conserved small side chain at position 4.53 within packing cluster 2 is shown to disrupt the structure of the visual receptor rhodopsin, whereas sites in packing cluster 1 (e.g., positions 1.46 and 2.47) are more tolerant to mutation but affect the overall stability of the protein. These findings reveal a common structural scaffold of GPCRs that is important for receptor folding and activation.

| S-EPMC5474883 | biostudies-literature

Within-subject variability in human retinal nerve fiber bundle width.

Project description:With the growing availability of high-resolution imaging there has been increased interest in developing new metrics for integrity of the retinal nerve fiber layer. In particular, it has been suggested that measurement of width of retinal nerve fiber bundles (RNFBs) may be useful in glaucoma, due to low between-subject variability in mean RNFB width. However, there have also been reports of substantial within-subject variability in the width of individual RNFBs. To assess within-subject variability as a potential source of selection bias in measurements of RNFB width, we used an adaptive optics scanning laser ophthalmoscope (AOSLO) to measure widths of individual RNFBs in one eye each of 11 young adults in good ocular health. In a pilot study we analyzed a large AOSLO image of RNFL in one participant then, based on those findings, in the main study we used AOSLO to image a smaller region in 10 additional healthy young adults. The pilot study of one eye found RNFB widths ranging from 10 μm to 44 μm. This suggested that biological variability was too high for measuring small changes arising from disease processes. This was confirmed in measurements of 10 eyes in the main study, RNFB widths ranged from 9 μm to 55 μm and every eye had large within-subject variability (exceeding 19 μm in all eyes) in RNFB width for nearby bundles. The within-subject variability in RNFB width, as well as variation in the width of single RNFBs over relatively short distances (<300 um) depending on the precise location of measurement, suggests that bundle width measurements would be highly susceptible to selection bias and therefore of limited clinical use.

| S-EPMC6795422 | biostudies-literature

Predicting acute kidney injury in cancer patients using heterogeneous and irregular data.

Project description:How can we predict the occurrence of acute kidney injury (AKI) in cancer patients based on machine learning with serum creatinine data? Given irregular and heterogeneous clinical data, how can we make the most of it for accurate AKI prediction? AKI is a common and significant complication in cancer patients, and correlates with substantial morbidity and mortality. Since no effective treatment for AKI still exists, it is important to take timely preventive measures. While several approaches have been proposed for predicting AKI, their scope and applicability are limited as they either assume regular data measured over a short hospital stay, or do not fully utilize heterogeneous data. In this paper, we provide an AKI prediction model with a greater applicability, which relaxes the constraints of existing approaches, and fully utilizes irregular and heterogeneous data for learning the model. In a cohort of 21,022 cancer patients who were registered into Korea Central Cancer Registry (KCCR) in Seoul National University Hospital between January 1, 2004 and December 31, 2013, our method achieves 0.7892 precision, 0.7506 recall, and 0.7576 F-measure in predicting whether a patient will develop AKI during the next 14 days.

| S-EPMC6053162 | biostudies-other

Colloidal gel elasticity arises from the packing of locally glassy clusters.

Project description:Colloidal gels formed by arrested phase separation are found widely in agriculture, biotechnology, and advanced manufacturing; yet, the emergence of elasticity and the nature of the arrested state in these abundant materials remains unresolved. Here, the quantitative agreement between integrated experimental, computational, and graph theoretic approaches are used to understand the arrested state and the origins of the gel elastic response. The micro-structural source of elasticity is identified by the l-balanced graph partition of the gels into minimally interconnected clusters that act as rigid, load bearing units. The number density of cluster-cluster connections grows with increasing attraction, and explains the emergence of elasticity in the network through the classic Cauchy-Born theory. Clusters are amorphous and iso-static. The internal cluster concentration maps onto the known attractive glass line of sticky colloids at low attraction strengths and extends it to higher strengths and lower particle volume fractions.

| S-EPMC6527676 | biostudies-other

Genome-wide analysis of local chromatin packing in Arabidopsis thaliana.

Project description:The spatial arrangement of interphase chromosomes in the nucleus is important for gene expression and genome function in animals and in plants. The recently developed Hi-C technology is an efficacious method to investigate genome packing. Here we present a detailed Hi-C map of the three-dimensional genome organization of the plant Arabidopsis thaliana. We find that local chromatin packing differs from the patterns seen in animals, with kilobasepair-sized segments that have much higher intrachromosome interaction rates than neighboring regions, representing a dominant local structural feature of genome conformation in A. thaliana. These regions, which appear as positive strips on two-dimensional representations of chromatin interaction, are enriched in epigenetic marks H3K27me3, H3.1, and H3.3. We also identify more than 400 insulator-like regions. Furthermore, although topologically associating domains (TADs), which are prominent in animals, are not an obvious feature of A. thaliana genome packing, we found more than 1000 regions that have properties of TAD boundaries, and a similar number of regions analogous to the interior of TADs. The insulator-like, TAD-boundary-like, and TAD-interior-like regions are each enriched for distinct epigenetic marks and are each correlated with different gene expression levels. We conclude that epigenetic modifications, gene density, and transcriptional activity combine to shape the local packing of the A. thaliana nuclear genome.

| S-EPMC4315298 | biostudies-literature

Dynamic and Irregular Distribution of RyR2 Clusters in the Periphery of Live Ventricular Myocytes.

Project description:Cardiac ryanodine receptors (RyR2s) are Ca2+ release channels clustering in the sarcoplasmic reticulum membrane. These clusters are believed to be the elementary units of Ca2+ release. The distribution of these Ca2+ release units plays a critical role in determining the spatio-temporal profile and stability of sarcoplasmic reticulum Ca2+ release. RyR2 clusters located in the interior of cardiomyocytes are arranged in highly ordered arrays. However, little is known about the distribution and function of RyR2 clusters in the periphery of cardiomyocytes. Here, we used a knock-in mouse model expressing a green fluorescence protein (GFP)-tagged RyR2 to localize RyR2 clusters in live ventricular myocytes by virtue of their GFP fluorescence. Confocal imaging and total internal reflection fluorescence microscopy was employed to determine and compare the distribution of GFP-RyR2 in the interior and periphery of isolated live ventricular myocytes and in intact hearts. We found tightly ordered arrays of GFP-RyR2 clusters in the interior, as previously described. In contrast, irregular distribution of GFP-RyR2 clusters was observed in the periphery. Time-lapse total internal reflection fluorescence imaging revealed dynamic movements of GFP-RyR2 clusters in the periphery, which were affected by external Ca2+ and RyR2 activator (caffeine) and inhibitor (tetracaine), but little detectable movement of GFP-RyR2 clusters in the interior. Furthermore, simultaneous Ca2+- and GFP-imaging demonstrated that peripheral RyR2 clusters with an irregular distribution pattern are functional with a Ca2+ release profile similar to that in the interior. These results indicate that the distribution of RyR2 clusters in the periphery of live ventricular myocytes is irregular and dynamic, which is different from that of RyR2 clusters in the interior.

| S-EPMC5984973 | biostudies-literature

Shaping micro-clusters via inverse jamming and topographic close-packing of microbombs.

Project description:Designing topographic clusters is of significant interest, yet it remains challenging as they often lack mobility or deformability. Here we exploit the huge volumetric expansion (up to 3000%) of a new type of building block, thermally expandable microbombs. They consist of a viscoelastic polymeric shell and a volatile gas core, which, within structural confinement, create micro-clusters via inverse jamming and topographical close-packing. Upon heating, microbombs anchored in rigid confinement underwent balloon-like blowing up, allowing for dense clusters via soft interplay between viscoelastic shells. Importantly, the confinement is unyielding against the internal pressure of the microbombs, thereby enabling self-assembled clusters, which can be coupled with topographic inscription to introduce structural hierarchy on the clusters. Our strategy provides densely packed yet ultralight clusters with a variety of complex shapes, cleavages, curvatures, and hierarchy. In turn, these clusters will enrich our ability to explore the assemblies of the ever-increasing range of microparticle systems.Self-assembled systems are normally composed of incompressible building blocks, which constrain their space filling efficiency. Yu et al. show programmable, densely packed clusters using thermally expandable soft microparticles, whereby the self-assembling process is realized via a jamming transition.

| S-EPMC5620065 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data