scholarly journals Principles of 3D Compartmentalization of the Human Genome

2020 ◽  
Author(s):  
Michael H. Nichols ◽  
Victor G. Corces
Keyword(s):  
Histone Modifications ◽  
Transcriptional Activity ◽  
Cell Types ◽  
Computer Simulation Model ◽  
Domain Formation ◽  
Biochemical Characteristics ◽  
Different Types ◽  
Nuanced Understanding ◽  
Fundamental Forces ◽  
Different Cell Types

AbstractChromatin is organized in the nucleus by CTCF loops and compartmental domains, the latter of which contain sequences bound by proteins capable of mediating interactions among themselves. While compartmental domains are one of the most prominent features of genome 3D organization at the chromosome scale, we lack a nuanced understanding of the different types of compartmental domains present in chromosomes and a mechanistic knowledge of the forces responsible for their formation. In this study, we compared different cell types to identify distinct paradigms of compartmental domain formation in human tissues. We identified and quantified compartmental forces correlated with histone modifications characteristic of transcriptional activity as well as previously underappreciated roles for compartmental domains correlated with the presence of H3K9me3, H3K27me3, or none of these histone modifications. We present a simple computer simulation model capable of predicting compartmental organization based on the biochemical characteristics of independent chromatin features. Using this computational model, we show that the underlying forces responsible for compartmental domain formation in human cells are conserved and that the diverse compartmentalization patterns seen across cells are due to differences in chromatin features. We extend these findings to Drosophila to suggest that the same fundamental forces are at work beyond humans. These results offer mechanistic insights into the fundamental forces driving the 3D organization of the genome.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 118-119
Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun
Keyword(s):  
Electron Microscopy ◽  
Structural Organization ◽  
Cell Types ◽  
Structural Features ◽  
Molecular Architecture ◽  
The Past ◽  
Keratin Filaments ◽  
Different Types ◽  
10 Nm Filaments ◽  
Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

scholarly journals Pancreatic α and β cells are globally phase-locked

2020 ◽  
Author(s):  
Huixia Ren ◽  
Yanjun Li ◽  
Chengsheng Han ◽  
Yi Yu ◽  
Bowen Shi ◽  
...  
Keyword(s):  
Islet Cells ◽  
Cell Types ◽  
Phase Oscillators ◽  
Β Cells ◽  
Oscillation Modes ◽  
Different Types ◽  
Glucagon And Insulin ◽  
Different Cell Types

ABSTRACTThe Ca2+ modulated pulsatile secretions of glucagon and insulin by pancreatic α and β cells play a key role in glucose metabolism and homeostasis. However, how different types of islet cells couple and coordinate via paracrine interactions to produce various Ca2+ oscillation patterns are still elusive. By designing a microfluidic device to facilitate long-term recording of islet Ca2+ activity at single cell level and simultaneously identifying different cell types in live islet imaging, we show heterogeneous but intrinsic Ca2+ oscillation patterns of islets upon glucose stimulation. The α and β cells oscillate in antiphase and are globally phase locked to various phase delays, causing fast, slow or mixed oscillations. A mathematical model of coupled phase oscillators quantitatively agrees with experiments and reveals the essential role of paracrine regulations in tuning the oscillation modes. Our study highlights the importance of cell-cell interactions to generate stable but tunable islet oscillation patterns.

Mucopolysaccharidosis in Adults

2016 ◽  
Author(s):  
Christian J. Hendriksz ◽  
Francois Karstens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Cell Types ◽  
Type Ii ◽  
System P ◽  
Different Types ◽  
The Central Nervous System ◽  
Different Cell Types

There are 8 different types of diseases of the mucopolysaccharides, each caused by a deficiency in one of 10 different enzymes involved in the degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate within the lysosomes of many different cell types and lead to clinical symptoms and excretion of large amounts of GAGs in the urine. Heritability is autosomal recessive except for MPS type II, which is X-linked. The disorders are chronic and progressive and, although the specific types all have their individual features, they share an abundance of clinical similarities. All involve the musculoskeletal, the cardiovascular, the pulmonary and the central nervous system.

scholarly journals Solitary Human Endogenous Retroviruses-K LTRs Retain Transcriptional Activity in Vivo, the Mode of Which Is Different in Different Cell Types

Virology ◽  
2001 ◽  
Vol 290 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Tatyana V. Vinogradova ◽  
Ludmila P. Leppik ◽  
Lev G. Nikolaev ◽  
Sergey B. Akopov ◽  
Anna M. Kleiman ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Cell Types ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Different Cell Types

scholarly journals The Histone Modification Code in the Pathogenesis of Autoimmune Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yasuto Araki ◽  
Toshihide Mimura
Keyword(s):  
Autoimmune Diseases ◽  
Histone Modifications ◽  
Lupus Erythematosus ◽  
Cell Types ◽  
Biliary Cirrhosis ◽  
Loss Of Self ◽  
Self Tolerance ◽  
Different Cell Types

Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases. Histone modifications regulate the chromatin states and gene transcription without any change in the DNA sequence, possibly resulting in phenotype alteration in several different cell types. In this paper, we discuss the significant roles of histone modifications involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, and type 1 diabetes.

scholarly journals Adiponectin: a pleiotropic hormone with multifaceted roles

2021 ◽  
Vol 67 (6) ◽  
pp. 98-112
Author(s):  
S. S. Shklyaev ◽  
G. A. Melnichenko ◽  
N. N. Volevodz ◽  
N. A. Falaleeva ◽  
S. A. Ivanov ◽  
...  
Keyword(s):  
Cell Types ◽  
The Body ◽  
Biologically Active ◽  
Protective Effects ◽  
Immune Functions ◽  
Ample Evidence ◽  
Endocrine Organs ◽  
Different Types ◽  
Different Cell Types ◽  
Pleiotropic Actions

Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called ‘adiponectin paradox’. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.

scholarly journals Mechanisms and Regulation of Cellular Senescence

2021 ◽  
Vol 22 (23) ◽  
pp. 13173
Author(s):  
Lauréline Roger ◽  
Fanny Tomas ◽  
Véronique Gire
Keyword(s):  
Dna Damage ◽  
Cellular Senescence ◽  
Cell Types ◽  
Feedback Loops ◽  
Cellular Structures ◽  
Damage Response ◽  
Different Types ◽  
Secretory Phenotype ◽  
Different Cell Types ◽  
Different Tissues

Cellular senescence entails a state of an essentially irreversible proliferative arrest in which cells remain metabolically active and secrete a range of pro-inflammatory and proteolytic factors as part of the senescence-associated secretory phenotype. There are different types of senescent cells, and senescence can be induced in response to many DNA damage signals. Senescent cells accumulate in different tissues and organs where they have distinct physiological and pathological functions. Despite this diversity, all senescent cells must be able to survive in a nondividing state while protecting themselves from positive feedback loops linked to the constant activation of the DNA damage response. This capacity requires changes in core cellular programs. Understanding how different cell types can undergo extensive changes in their transcriptional programs, metabolism, heterochromatin patterns, and cellular structures to induce a common cellular state is crucial to preventing cancer development/progression and to improving health during aging. In this review, we discuss how senescent cells continuously evolve after their initial proliferative arrest and highlight the unifying features that define the senescent state.

scholarly journals Sequence determinants of human gene regulatory elements

2021 ◽  
Author(s):  
Biswajyoti Sahu ◽  
Tuomo Hartonen ◽  
Paivi Pihlajamaa ◽  
Bei Wei ◽  
Kashyap Dave ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcriptional Activity ◽  
Cell Types ◽  
Regulatory Elements ◽  
Binding Motif ◽  
Atomic Unit ◽  
Gene Regulatory Elements ◽  
A Cell ◽  
Different Cell Types

DNA determines where and when genes are expressed, but the full set of sequence determinants that control gene expression is not known. To obtain a global and unbiased view of the relative importance of different sequence determinants in gene expression, we measured transcriptional activity of DNA sequences that are in aggregate ~100 times longer than the human genome in three different cell types. We show that enhancers can be classified to three main types: classical enhancers1, closed chromatin enhancers and chromatin-dependent enhancers, which act via different mechanisms and differ in motif content. Transcription factors (TFs) act generally in an additive manner with weak grammar, with classical enhancers increasing expression from promoters by a mechanism that does not involve specific TF-TF interactions. Few TFs are strongly active in a cell, with most activities similar between cell types. Chromatin-dependent enhancers are enriched in forkhead motifs, whereas classical enhancers contain motifs for TFs with strong transactivator domains such as ETS and bZIP; these motifs are also found at transcription start site (TSS)-proximal positions. However, some TFs, such as NRF1 only activate transcription when placed close to the TSS, and others such as YY1 display positional preference with respect to the TSS. TFs can thus be classified into four non-exclusive subtypes based on their transcriptional activity: chromatin opening, enhancing, promoting and TSS determining factors — consistent with the view that the binding motif is the only atomic unit of gene expression.

scholarly journals Constitutive Activation of Chaperone-mediated Autophagy in Cells with Impaired Macroautophagy

2008 ◽  
Vol 19 (5) ◽  
pp. 2179-2192 ◽  
Author(s):  
Susmita Kaushik ◽  
Ashish C. Massey ◽  
Noboru Mizushima ◽  
Ana Maria Cuervo
Keyword(s):  
Cross Talk ◽  
Mammalian Cells ◽  
Cell Types ◽  
Stress Conditions ◽  
Different Types ◽  
Direct Cross ◽  
Related Proteins ◽  
Different Cell Types ◽  
Work Supports ◽  
Chaperone Mediated Autophagy

Three different types of autophagy—macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA)—contribute to degradation of intracellular components in lysosomes in mammalian cells. Although some level of basal macroautophagy and CMA activities has been described in different cell types and tissues, these two pathways are maximally activated under stress conditions. Activation of these two pathways is often sequential, suggesting the existence of some level of cross-talk between both stress-related autophagic pathways. In this work, we analyze the consequences of blockage of macroautophagy on CMA activity. Using mouse embryonic fibroblasts deficient in Atg5, an autophagy-related protein required for autophagosome formation, we have found that blockage of macroautophagy leads to up-regulation of CMA, even under basal conditions. Interestingly, different mechanisms contribute to the observed changes in CMA-related proteins and the consequent activation of CMA during basal and stress conditions in these macroautophagy-deficient cells. This work supports a direct cross-talk between these two forms of autophagy, and it identifies changes in the lysosomal compartment that underlie the basis for the communication between both autophagic pathways.

scholarly journals Apoptotic Bodies: Particular Extracellular Vesicles Involved in Intercellular Communication

Biology ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 21 ◽  
Author(s):  
Michela Battistelli ◽  
Elisabetta Falcieri
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Genetic Information ◽  
Cell Communication ◽  
Cell Types ◽  
Apoptotic Bodies ◽  
Species Barrier ◽  
Physiological Conditions ◽  
Different Types ◽  
Different Cell Types

In the last decade, a new method of cell–cell communication mediated by membranous extracellular vesicles (EVs) has emerged. EVs, including exosomes, microvesicles, and apoptotic bodies (ApoBDs), represent a new and important topic, because they are a means of communication between cells and they can also be involved in removing cellular contents. EVs are characterized by differences in size, origin, and content and different types have different functions. They appear as membranous sacs released by a variety of cells, in different physiological and patho-physiological conditions. Intringuingly, exosomes and microvesicles are a potent source of genetic information carriers between different cell types both within a species and even across a species barrier. New, and therefore still relatively poorly known vesicles are apoptotic bodies, on which numerous in-depth studies are needed in order to understand their role and possible function. In this review we would like to analyze their morpho-functional characteristics.

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