scholarly journals 19. GENETIC RISK ARCHITECTURE OF SCHIZOPHRENIA AND THREE-DIMENSIONAL CHROMATIN DYNAMICS ACROSS NEUROTRANSMITTER SYSTEMS

2021 ◽  
Vol 51 ◽  
pp. e50
Author(s):  
Samuel Powell ◽  
Callan O'Shea ◽  
Kayla Townsley ◽  
Kristina Dobrindt ◽  
Rahat Elahi ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Three Dimensional ◽  
Neurotransmitter Systems ◽  
Chromatin Dynamics

scholarly journals Chromosome-wide co-fluctuation of stochastic gene expression in mammalian cells

2019 ◽  
Author(s):  
Mengyi Sun ◽  
Jianzhi Zhang
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Three Dimensional ◽  
Sequencing Data ◽  
Chromatin Dynamics ◽  
Gene Expression Noise ◽  
Genes Encoding ◽  
The Face ◽  
Allele Specific ◽  
Genomic Scale

ABSTRACTGene expression is subject to stochastic noise, but to what extent and by which means such stochastic variations are coordinated among different genes are unclear. We hypothesize that neighboring genes on the same chromosome co-fluctuate in expression because of their common chromatin dynamics, and verify it at the genomic scale using allele-specific single-cell RNA-sequencing data of mouse cells. Unexpectedly, the co-fluctuation extends to genes that are over 60 million bases apart. We provide evidence that this long-range effect arises in part from chromatin co-accessibilities of linked loci attributable to three-dimensional proximity, which is much closer intra-chromosomally than inter-chromosomally. We further show that genes encoding components of the same protein complex tend to be chromosomally linked, likely resulting from natural selection for intracellular among-component dosage balance. These findings have implications for both the evolution of genome organization and optimal design of synthetic genomes in the face of gene expression noise.

scholarly journals Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

2020 ◽  
Author(s):  
Lei Chang ◽  
Mengfan Li ◽  
Shipeng Shao ◽  
Chen Li ◽  
Shanshan Ai ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Three Dimensional ◽  
Higher Order ◽  
Order Structure ◽  
Chromatin Dynamics ◽  
Lamin B1 ◽  
Chromatin Architecture ◽  
Chromatin Interactions ◽  
Molecular Machinery

Abstract The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.

scholarly journals From enhanceropathies to the epigenetic manifold underlying human cognition

2019 ◽  
Vol 28 (R2) ◽  
pp. R226-R234 ◽  
Author(s):  
Alessandro Vitriolo ◽  
Michele Gabriele ◽  
Giuseppe Testa
Keyword(s):  
Target Genes ◽  
Three Dimensional ◽  
Autism Spectrum ◽  
Adult Brain ◽  
Human Cognition ◽  
Regulatory Regions ◽  
Chromatin Dynamics ◽  
Cellular Models ◽  
Technological Advances

Abstract A vast portion of intellectual disability and autism spectrum disorders is genetically caused by mutations in chromatin modulators. These proteins play key roles in development and are also highly expressed in the adult brain. Specifically, the pivotal role of chromatin regulation in transcription has placed enhancers at the core of neurodevelopmental disorders (NDDs) studies, ushering in the coining of the term enhanceropathies. The convergence of these disorders is multilayered, spanning from molecular causes to pathophysiological traits, including extensive overlaps between enhanceropathies and neurocristopathies. The reconstruction of epigenetic circuitries wiring development and underlying cognitive functions has gone hand in hand with the development of tools that increase the sensitivity of identifying regulatory regions and linking enhancers to their target genes. The available models, including loop extrusion and phase separation, have been bringing into relief complementary aspects to interpret gene regulation datasets, reinforcing the idea that enhancers are not all the same and that regulatory regions possess shades of enhancer-ness and promoter-ness. The current limits in enhancer definition, within the emerging broader understanding of chromatin dynamics in time and space, are now on the verge of being transformed by the possibility to interrogate developmentally relevant three-dimensional cellular models at single-cell resolution. Here we discuss the contours of how these technological advances, as well as the epistemic limitations they are set to overcome, may well usher in a change of paradigm for NDDs, moving the quest for convergence from enhancers to the four-dimensional (4D) genome.

scholarly journals Origin of Genome Instability and Determinants of Mutational Landscape in Cancer Cells

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1101
Author(s):  
Sonam Mehrotra ◽  
Indraneel Mittra
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Genome Instability ◽  
Three Dimensional ◽  
Tumor Formation ◽  
Dna Lesions ◽  
Early Event ◽  
Chromatin Dynamics ◽  
Cellular Processes ◽  
New Biomarkers

Genome instability is a crucial and early event associated with an increased predisposition to tumor formation. In the absence of any exogenous agent, a single human cell is subjected to about 70,000 DNA lesions each day. It has now been shown that physiological cellular processes including DNA transactions during DNA replication and transcription contribute to DNA damage and induce DNA damage responses in the cell. These processes are also influenced by the three dimensional-chromatin architecture and epigenetic regulation which are altered during the malignant transformation of cells. In this review, we have discussed recent insights about how replication stress, oncogene activation, chromatin dynamics, and the illegitimate recombination of cell-free chromatin particles deregulate cellular processes in cancer cells and contribute to their evolution. The characterization of such endogenous sources of genome instability in cancer cells can be exploited for the development of new biomarkers and more effective therapies for cancer treatment.

scholarly journals The lncRNA APOLO interacts with the transcription factor WRKY42 to trigger root hair cell expansion in response to cold

2020 ◽  
Author(s):  
Michaël Moison ◽  
Javier Martínez Pacheco ◽  
Leandro Lucero ◽  
Camille Fonouni-Farde ◽  
Johan Rodríguez-Melo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Root Hair ◽  
Low Temperatures ◽  
Cell Expansion ◽  
Growth And Development ◽  
Transcriptional Activity ◽  
Three Dimensional ◽  
Noncoding Rnas ◽  
Chromatin Dynamics ◽  
Root Hair Cell

ABSTRACTPlant long noncoding RNAs (lncRNAs) have emerged as important regulators of chromatin dynamics, impacting on transcriptional programs leading to different developmental outputs. The lncRNA AUXIN REGULATED PROMOTER LOOP (APOLO) directly recognizes multiple independent loci across the Arabidopsis genome and modulates their three-dimensional chromatin conformation, leading to transcriptional shifts. Here, we show that APOLO recognizes the locus encoding the root hair (RH) master regulator ROOT HAIR DEFECTIVE 6 (RHD6) and controls RHD6 transcriptional activity leading to cold-enhanced RH elongation. Furthermore, we demonstrate that APOLO interacts with the transcription factor WRKY42 and modulates its binding to the RHD6 promoter. WRKY42 is required for the activation of RHD6 by low temperatures and WRKY42 deregulation impairs cold-induced RH expansion. Collectively, our results indicate that a novel ribonucleoprotein complex involving APOLO and WRKY42 forms a regulatory hub which activates RHD6 by shaping its epigenetic environment and integrates signals governing RH growth and development.

scholarly journals Unraveling three-dimensional chromatin structural dynamics during spermatogonial differentiation

2021 ◽  
Author(s):  
Yi Zheng ◽  
Lingkai Zhang ◽  
Long Jin ◽  
Pengfei Zhang ◽  
Fuyuan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Three Dimensional ◽  
Higher Order ◽  
Self Renewal ◽  
Chromosome Conformation ◽  
Chromatin Dynamics ◽  
Chromatin Architecture ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Chromatin Structural

Spermatogonial stem cells (SSCs) are able to undergo self-renewal and differentiation. Unlike the self-renewal that replenishes the SSC and progenitor pool, the differentiation is an irreversible process committed to meiosis. While the preparations for meiotic events in differentiating spermatogonia (Di-SG) are likely to be accompanied by alterations in chromatin structure, the three-dimensional (3D) chromatin architectural difference between SSCs and Di-SG, and the higher-order chromatin dynamics during spermatogonial differentiation, have not been systematically investigated. Here, we performed in situ high throughput chromosome conformation capture (Hi-C), RNA-sequencing (RNA-seq) and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses on porcine undifferentiated spermatogonia (Un-SG, which consist of SSCs and progenitors) and Di-SG. By integrating and analyzing these data, we identified that Di-SG exhibited increased disorder but weakened compartmentalization and topologically associating domains (TADs) in comparison with Un-SG, suggesting that diminished higher-order chromatin architecture in meiotic cells, as shown by recent reports, is preprogramed in Di-SG. Our data also revealed that A/B compartments and TADs were related to dynamic gene expression during spermatogonial differentiation. We further unraveled the contribution of promoter-enhancer interactions (PEIs) to pre-meiotic transcriptional regulation, which has not been accomplished in previous studies due to limited cell input and resolution. Together, our study uncovered the 3D chromatin structure of SSCs/progenitors and Di-SG, as well as the interplay between higher-order chromatin architecture and dynamic gene expression during spermatogonial differentiation, providing novel insights into the mechanisms for SSC self-renewal and differentiation and having implications for diagnosis and treatment of male sub-/infertility.

The orbit of Pluto over a long interval of time

1966 ◽  
Vol 25 ◽  
pp. 227-229 ◽  
Author(s):  
D. Brouwer
Keyword(s):  
Periodic Orbit ◽  
Numerical Integration ◽  
Restricted Problem ◽  
Three Dimensional ◽  
The Third ◽  
Circular Restricted Problem ◽  
Resonance Relation

The paper presents a summary of the results obtained by C. J. Cohen and E. C. Hubbard, who established by numerical integration that a resonance relation exists between the orbits of Neptune and Pluto. The problem may be explored further by approximating the motion of Pluto by that of a particle with negligible mass in the three-dimensional (circular) restricted problem. The mass of Pluto and the eccentricity of Neptune's orbit are ignored in this approximation. Significant features of the problem appear to be the presence of two critical arguments and the possibility that the orbit may be related to a periodic orbit of the third kind.

Sign in / Sign up

Export Citation Format

Share Document