Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chromatin conformation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

Structural basis of differential gene expression at eQTLs loci from high-resolution ensemble models of 3D single-cell chromatin conformations.

MOTIVATION: Techniques such as high-throughput chromosome conformation capture (Hi-C) have provided a wealth of information on nucleus organization and genome important for understanding gene expression regulation. Genome-Wide Association Studies have identified numerous loci associated with complex traits. Expression quantitative trait loci (eQTL) studies have further linked the genetic variants to alteration in expression levels of associated target genes across individuals. However, the functional roles of many eQTLs in noncoding regions remain unclear. Current joint analyses of Hi-C and eQTLs data lack advanced computational tools, limiting what can be learned from these data. RESULTS: We developed a computational method for simultaneous analysis of Hi-C and eQTL data, capable of identifying a small set of nonrandom interactions from all Hi-C interactions. Using these nonrandom interactions, we reconstructed large ensembles (×105) of high-resolution single-cell 3D chromatin conformations with thorough sampling, accurately replicating Hi-C measurements. Our results revealed many-body interactions in chromatin conformation at the single-cell level within eQTL loci, providing a detailed view of how 3D chromatin structures form the physical foundation for gene regulation, including how genetic variants of eQTLs affect the expression of associated eGenes. Furthermore, our method can deconvolve chromatin heterogeneity and investigate the spatial associations of eQTLs and eGenes at subpopulation level, revealing their regulatory impacts on gene expression. Together, ensemble modeling of thoroughly sampled single-cell chromatin conformations combined with eQTL data, helps decipher how 3D chromatin structures provide the physical basis for gene regulation, expression control, and aid in understanding the overall structure-function relationships of genome organization. AVAILABILITY AND IMPLEMENTATION: It is available at https://github.com/uic-liang-lab/3DChromFolding-eQTL-Loci.

Quantitative Trait Loci↗
PubMed1979

Altered chromatin conformation in Alzheimer's disease.

Chromatin samples were prepared from forty human brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Employing a bacterial RNA polymerase as probe, only the euchromatin fractions were capable of RNA synthesis. In Control human brains, in brains of patients with dialysis dementia and in brains of elderly individuals without or with dementia of a type other than Alzheimer's disease, the euchromatin fractions accounted for about 75 per cent of the total DNA. In contrast, in brains of patients with advanced senile dementia or presenile dementia of the Alzheimer type, a wide range of euchromatin content was encountered with an average value of 55 per cent. Heterochromatization occurred in both neuron and glia enriched fractions suggesting that a major alteration in protein metabolism occurs in Alzheimer's disease.

Aged↗
PubMed1979

Chromatin conformation during cell differentiation of human myeloid leukemia cells.

A novel human promyelocytic leukemia cell line (HL-60) has been shown to form terminally differentiated granulocytes in the presence of dimethyl-sulfoxide (DMSO), some other chemicals, or colony stimulating factor. Compared to chromatin from HL-60 cells, chromatin from DMSO treated HL-60 cells showed an enrichment in low temperature melting material. The decrease in thermostability of chromatin from HL-60 cells after DMSO treatment is similar to the shift in thermostability of chromatin from human lymphocytes after stimulation with phytohemagglutinin (PHA). These results suggest that changes in the thermostability of chromatin may not be specific for cell differentiation or PHA stimulation.

Adult↗
PubMed1976

Organization of DNA in chromatin.

Conformational changes in DNA that accompany drug intercalation have led us to ask if DNA first bends or "kinks" to accept an intercalative drug or dye. Kinking is made possible by altering the normal C2' endo deoxyribose sugar ring puckering in B DNA to a mixed sugar puckering pattern of the type C3' and partially unstacking base-pairs. A kinking scheme such as this would require minimal stereochemical rearrangement and would also involve small energies. This has prompted us to ask more generally if a conformational change such as this could be used by proteins in their interactions with nucleic acids. In this papter we describe an interesting superhelical DNA structure formed by kinking DNA every 10 base-pairs. The structure may be used in the organization of DNA in chromatin.

Chemical Phenomena↗
PubMed2025

Genome topology analysis and transcriptomics of human osteoclasts reveals enhancer-promoter interactions at loci for bone traits and diseases.

Genome-wide association studies (GWAS) relevant to osteoporosis have identified hundreds of loci; however, understanding how these variants influence the phenotype is complicated because most reside in non-coding DNA sequence that serves as transcriptional enhancers and repressors. To advance knowledge on these regulatory elements in osteoclasts (OCs), we performed Micro-C analysis, which informs on the genome topology of these cells and integrated the results with transcriptome and GWAS data to further define loci linked to BMD. Using blood cells isolated from 4 healthy participants aged 31-61 yr, we cultured OC in vitro and generated a Micro-C chromatin conformation capture dataset. We characterized chromatin loops (CLs) in OC from among more than 69 million chromatin interactions identified in the genome. Of the CL identified in OC, >16 000 were unique compared to precursor cells. When sentinel single nucleotide polymorphisms from osteoporosis and bone-related GWAS and those in linkage disequilibrium at r 2 > 0.6 were mapped to CL for OC, 12 588 of these variants were observed within chromatin contact regions. Notable in differential gene ontology enrichment analyses of the topology data for OC and precursors were pathways regulating pluripotency of stem cells, Wnt signaling, nucleotide-binding oligomerization domain (NOD)-like receptor signaling and chemokine signaling. These data, in combination with other 3D genome architecture and epigenetic data (eg, histone modifications and chromatin accessibility), will be useful in modeling to predict genome-wide, which enhancers regulate which genes in OC. This data will therefore also be informative for resolving GWAS hits. In conclusion, we have generated a high-resolution genome topology dataset for human OC and have used this to identify CLs relevant to studies of the genetics of osteoporosis. This data will serve as a powerful resource to inform future functional studies of OC biology.

BMD↗
PubMed1975

A contribution of nonhistone proteins to the conformation of chromatin.

1. Changes in circular dichroism (CD) spectra and thermal melting profiles of guinea pigliver DNA reassociated with histones and/or nonhistone proteins from the cerebral of liver chromatin are described. 2. In the DNA-histone complex, positive ellipiticity in the CD spectrum at 260-300 nm is progressively lod by a red-shift of the crossover point at around 260 nm. DNA in this complex is thermally stabilised to a considerable extent, but not to such a full extent as is shown with DNA in native chromatin. 3. DNA-nonhistone complex in 0.14 M NaCl is, in contrast to DNA-histone complex, not precipitable by centrifugation at 20 000 X g. DNA in this complex shows only a slight reduction in ellipticity at 260-300 nm, and a very weak thermal stabilisation. 4. Characteristics in the CD spectrum of the native chromatin are most satisfactorily reproduced in the DNA-histone-nonhistone complex. These include a large decrease in ellipticity at 260-300 nm, a red-shift of the crossover point at around 260 nm, and a slight negative band at around 305 nm. Also, DNA in this complex is thermally stabilised to the extent comparable with DNA in the native chromatin. 5. Addition of nonhistone proteins to the preformed DNA-histone complex in 3 M urea renders a half of the complex, named DNA-histone(-nonhistone), unprecipitable upon centrifugation at 20 000 X g in 0.14 M NaCl. CD spectrum and thermal melting profile of the precipitable DNA-histone(-nonhistone) complex are similar to those of the DNA-histone-nonhistone complex, while in the unprecipitable DNA-histone(-nonhistone) comples, the ellipticity at 260-300 nm is significantly elevated and the highest melting transition (at 80 degrees C) is lacking. 6. The CD spectrum of native cerebral chromatin closely resembles that of unprecipitable DNA-histone(-nonhistone) complex, while in liver chromatin, the spec.trum is an intermediate between those of the unprecipitable and pn of chromatin by nonhistone proteins. Cerebral nonhistone proteins bind to DNA and to the DNA-histone complex more extensively than liver nonhistone proteins. 7. It is concluded that, although the basic conformation of DNA in native chromatin is determined largely by histones, nonhistone proteins also play an individual role. There is also an indication that nonhistone proteins exert an organ-specific modification of chromatin superstructure.

Animals↗
PubMed1977

Genes transcribed at diverse rates have a similar conformation in chromatin.

We have analyzed the DNA generated upon treatment of oviduct nuclei with pancreatic DNase I (deoxyribonucleate 3'-oligonucleotidohydrolase; EC 3.1.4.6), with cDNA copies of specific mRNA sequences to study the structure and organization of transcriptionally active genes in chromatin. In this report we examine the kinetics of digestion of three classes of genes in the oviduct which are transcribed at significantly different rates. Our results indicate that the ovalbumin genes appear to be organized by chromatin proteins in such a way that they are rendered exceedingly sensitive to digestion by DNase I. This sensitivity is not observed in the liver, a tissue in which these genes are transcriptionally inert. Furthermore, the transcriptionally inactive globin genes in the oviduct are not selectively sensitive to nuclease attack and are digested 5 times more slowly in the ovalbumin genes in this tissue. In addition, we have examined the accessibility of a complex subset of genes that are rarely represented in the mRNA and are likely to be transcribed at a frequency orders of magnitude below that of the ovalbumin gene. Comparison of the accessibility of these sequences with that of the ovalbumin gene indicates that these two subsets of genes are recognized and cleaved by DNase I at similar rates. These results suggest that the maintenance of an active conformation about specific genes does not reflect the polymerase distribution about these genes. This active conformation is therefore not confined to sequences actively engaged in the transcription process and may reflect the structure about a subpopulation of the genome which represents the transcriptional potential of a given cell type.

Animals↗
PubMed1975

Studies on the role and mode of operation of the very-lysine-rich histone H1 (F1) in eukaryote chromatin. The conformation of histone H1.

Proton magnetic resonance, circular dichroism and other studies of whole and cleaved calf thymus histone H1 (formerly F1) reveal the presence of specific folded structures in the region approximately from residue 40--115. Ionic, hydrogen-bond and hydrophobic interactions all appear to contribute to the stability of the structure, which is predicted to contain alpha-helices in regions 42--55 and 58--75. No evidence was found for beta-structures, either inter or intramolecular, or for any structure formation outside the region 40--115. At 18 degrees C and a protein concentration of 2 mM the first-order exchange rate between random-coil and structured forms is slower than 80 s-1; at 40 degrees C the exchange rate is faster than 330 s-1.

Animals↗
PubMed1979

Electric birefringence of DNA and chromatin. Influence of divalent cations.

The effects of divalent cations on the DNA and chromatin conformation have been investigated by electric birefringence and birefringence relaxation measurements at low and constant ionic strength (0.001). An important decrease of the intrinsic optical anisotropy of DNA has been found in the presence of Mn2+ and Cu2+, but not with Mg2+. A complex variation of the mean relaxation time with the ratio I/P of ion to DNA-phosphate molar concentration has been evidenced in the presence of Mn2+ and Cu2+, while the mean relaxation time monotonously decreased in the presence of Mg2+. These observations are interpreted in terms of a specific organization of DNA in a compact, rigid structure, in the presence of Mn2+ and Cu2+, and a non-specific coiling in the presence of Mg2+. Drastic conformational changes encountered by chromatin in the presence of Mg2+ and Mn2+ cations have also been evidenced through electric birefringence measurements. They are interpreted by the formation of a superhelical compact arrangement of nucleosome strings which yielded a reversal of the birefringence sign with respect to the negative anisotropy observed in the presence of Na+ ions. The removal of the histone H1 prevented the appearance of this quaternary structure. More extended fragments of the chromatin chain obtained by ECTHAM chromatography of sonicated chromatin could not afford such compact arrangements.

Birefringence↗
PubMed1975

Studies on the role and mode of operation of the very-lysine-rich histones in eukaryote chromatin. The conformation of phi1 histones from marine invertebrate sperm.

Proton magnetic resonance, circular dichroism and infrared spectroscopy are used to investigate the secondary and tertiary structure of three very lysine-rich histones from marine invertebrate sperm. At high ionic strength both Arbacia lixula and Holothuria tubulosa histone phi 1 are observed to contain 25-30% alpha-helix, no beta-structure and to form specific folded structures. Both phi 1 proton magnetic resonance spectra have perturbed methyl resonances at chemical shifts close to those observed for calf thymus H1, suggesting analogies in tertiary structure. Mytilus edulis histone phi 1 however, shows no spectroscopic evidence of secondary and tertiary structure on salt addition.

Amino Acids↗
PubMed2025

Significance in scale space for Hi-C data.

MOTIVATION: Hi-C technology has been developed to profile genome-wide chromosome conformation. So far Hi-C data have been generated from a large compendium of different cell types and different tissue types. Among different chromatin conformation units, chromatin loops were found to play a key role in gene regulation across different cell types. While many different loop calling algorithms have been developed, most loop callers identified shared loops as opposed to cell-type-specific loops. RESULTS: We propose SSSHiC, a new loop calling algorithm based on significance in scale space, which can be used to understand data at different levels of resolution. By applying SSSHiC to neuronal and glial Hi-C data, we detected more loops that are potentially engaged in cell-type-specific gene regulation. Compared with other loop callers, such as Mustache, these loops were more frequently anchored to gene promoters of cellular marker genes and had better APA scores. Therefore, our results suggest that SSSHiC can effectively capture loops that contain more gene regulatory information. AVAILABILITY AND IMPLEMENTATION: The Hi-C data used in this study can be accessed through the PsychENCODE Knowledge Portal at https://www.synapse.org/#! Synapse: syn21760712. The code utilized for Curvature SSS cited in this study is available at https://github.com/jsmarron/MarronMatlabSoftware/blob/master/Matlab9/Matlab9Combined.zip. All custom code used in this research can be found in the GitHub repository: https://github.com/jerryliu01998/HiC. The code has also been submitted to Code Ocean with the doi: 10.24433/CO.1912913.v1.

Algorithms↗
PubMed2026

ONT-only genome assembly of a Korean male individual using a semen sample.

BACKGROUND: Long-read sequencing has enabled the generation of high-quality human genome assemblies, but many previous assemblies were based on blood-derived DNA and often relied on limited data types from a single sequencing strategy. OBJECTIVE: This study aimed to generate high-quality phased genome assemblies of a Korean individual using multiple independent long-read datasets produced from a single sequencing platform and to evaluate their utility for chromosome-scale assembly and variant detection. METHODS: Genomic DNA was extracted from a semen sample of a Korean male. Long-read, ultra-long-read, and chromatin conformation capture sequencing data were generated using Oxford Nanopore Technologies. These datasets were integrated to construct phased genome assemblies, followed by correction of noticeable phasing errors and assessment of assembly continuity, chromosomal representation, telomeric repeat recovery, and variant detection performance. RESULTS: The final phased assemblies spanned approximately 2.9 Gb and represented 23 pairs of chromosomes with an NG50 of 150 Mb. Telomeric repeats were detected at 36 and 37 of the 48 chromosomal ends in the two assemblies, indicating high end-to-end completeness. In addition, we successfully identified structural variants, including small variants. These results demonstrate that combining multiple Oxford Nanopore data types can produce highly continuous and informative phased human genome assemblies. CONCLUSIONS: We generated high-quality phased genome assemblies of a Korean individual using Oxford Nanopore long-read sequencing data derived from semen DNA. This publicly available genome resource will support broader applications of long-read sequencing in human genomics and variant analysis.

Humans↗
PubMed2026

One chromatin, many structures: From ensemble contact maps to single-cell 3D organization.

Understanding how chromatin folds in three dimensions remains challenging because most experimental assays capture low-dimensional projections of an underlying, highly heterogeneous polymer. Here, we present an ensemble-based interpretive framework built on the previously introduced Self-Returning Excluded Volume (SR-EV) model, a minimal generator of chromatin conformations using a nucleosome-indexed coarse-grained representation based on stochastic return rules and excluded-volume geometry. Despite its simplicity, SR-EV recapitulates key experimental signatures across scales: heterogeneous nanoscale packing domains resembling ChromEMT and ChromSTEM observations, sparse and highly variable single-configuration contact patterns analogous to single-cell chromosome conformation capture (Hi-C), and robust ensemble-level contact enrichment consistent with topologically associating domains (TADs). In this framework, Hi-C loop and TAD signatures are interpreted as ensemble-level statistical enrichments rather than invariant features of single-cell conformations. SR-EV is explicitly designed to generate large ensembles of complete three-dimensional chromatin configurations that can be projected consistently onto two-dimensional contact maps and one-dimensional genomic profiles. By introducing architectural-protein effects only through ensemble selection rather than explicit forces, SR-EV supports a separation between intrinsic polymer geometry and regulatory bias and suggests that TAD-like features can emerge as statistical enrichments rather than deterministic three-dimensional structures. Coordination number and probe-based accessibility computed directly from SR-EV provide a unified link between three-dimensional packing, two-dimensional contact maps, and one-dimensional genomic profiles. The main contribution of this work is to show, within a single coarse-grained framework, how these multimodal observables arise as linked projections of the same heterogeneous chromatin ensemble through averaging and conditional sampling. Together, these results establish SR-EV as a minimal and geometrically grounded mesoscale reference framework for interpreting how heterogeneous chromatin ensembles give rise to multimodal experimental observables while remaining consistent with the fact that chromatin organization is realized in individual cells.

Chromatin↗
PubMed2026

Haplotype-resolved 3D genome maps reveal RNAPII-mediated allelic regulation in hybrid rice.

To understand how the two parental genomes coordinate transcription in hybrids, chromatin architecture must be resolved at the haplotype level. Here, using phased Bridge-Linker Hi-C, we reconstructed a haplotype-resolved three-dimensional (3D) genome of the elite hybrid rice (Oryza sativa) line Shanyou 63 (SY63). We identified extensive allele-specific chromatin conformations. Furthermore, we generated allele-resolved RNAPII ChIA-PET maps and phased transcriptomes to explore how chromatin interactions contribute to allelic regulation. Although maternal and paternal homologs share broadly similar chromatin features, we detected widespread haplotype-biased RNAPII binding and chromatin looping at high resolution. These allele-specific RNAPII-mediated contacts were significantly associated with biased expression. Stronger RNAPII binding on one haplotype promoted the formation of long-range regulatory loops with distal genes, thereby contributing to allele-biased transcription at a subset of loci, even when promoter-proximal RNAPII occupancy was comparable between alleles. These results demonstrate that subtle differences in RNAPII engagement and 3D regulatory wiring between parental haplotypes can reshape transcriptional output in hybrids, providing new insights into the mechanisms underlying the allelic regulation of gene expression.

Allele-specific chromatin interactions↗
PubMed2025

Effects of Lamina-Chromatin Attachment on Super Long-Range Chromatin Interactions.

The interactions between chromatin and lamin proteins localized on the nuclear envelope play a crucial role in the three-dimensional (3D) organization of the genome. This study investigates the influence of lamin associated domains (LADs) on genome organization at the chromosome level using 3D polymer models of mouse embryonic fibroblasts (MEFs) and embryonic stem cells (mESCs). By integrating genome-wide LAD maps from DamID assays, we simulated chromatin conformations with and without LAD attachment to the nuclear envelope. Our results show that incorporating LAD-lamin interactions yields a radial chromatin distribution consistent with experimental observations. Moreover, LAD-lamin interactions induce significant super long-range chromatin contacts across distant genomic regions. These findings suggest two distinct mechanisms driving induction of chromatin interactions by LAD-lamin attachment.

3D single cell conformations↗