Mechanical Forces in Nuclear Organization

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 14(1), P. a039685 - a039685

Published: June 29, 2021

Yekaterina A. Miroshnikova1,2,3,4,5 and Sara Wickström1,2,3,4,6 1Helsinki Institute of Life Science, Biomedicum Helsinki, University Helsinki 00014, Finland 2Wihuri Research Institute, 00290, 3Stem Cells Metabolism Program, Faculty Medicine, 4Max Planck for Biology Ageing, Cologne 50931, Germany 5Laboratory Molecular Biology, National Diabetes Digestive Kidney Diseases, Institutes Health, Bethesda, Maryland 20892, USA 6Cluster Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Correspondence: yekaterina.miroshnikova{at}helsinki.fi; sara.wickstrom{at}helsinki.fi

Language: Английский

---

Destabilizing heterochromatin by APOE mediates senescence

Nature Aging, Journal Year: 2022, Volume and Issue: 2(4), P. 303 - 316

Published: March 28, 2022

Language: Английский

---

Molecular and Cellular Bases of Lipodystrophy Syndromes

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 3, 2022

Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results heterogeneous genetic acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions the gonadotropic axis and endocrine defects leptin adiponectin deficiency. Diagnosis, based on clinical investigations, analyses, is major importance adapt medical care counseling. Molecular cellular bases these involve, among others, altered adipocyte differentiation, structure and/or regulation lipid droplet, premature senescence. frequently present as systemic multi-tissue involvement. After an update main molecular forms lipodystrophy, we will focus topics that have recently emerged in field. We discuss links between lipodystrophy ageing immuno-inflammatory aggressions tissue, well relationships lipomatosis lipodystrophy. Finally, indications substitutive therapy metreleptin, analog leptin, which approved Europe USA, be discussed.

Language: Английский

---

The Nuclear Lamina

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 14(2), P. a040113 - a040113

Published: Aug. 16, 2021

Xianrong Wong1, Ashley J. Melendez-Perez2 and Karen L. Reddy2,3 1Laboratory of Developmental Regenerative Biology, Skin Research Institute Singapore, Agency for Science, Technology (A∗STAR), Singapore 138648 2Department Biological Chemistry Center Epigenetics, Johns Hopkins University Medicine, Baltimore, Maryland 21205, USA 3Sidney Kimmel Cancer Institute, School 21231, Correspondence: kreddy4{at}jhmi.edu

Language: Английский

---

Lamina-associated domains: Tethers and looseners

Current Opinion in Cell Biology, Journal Year: 2022, Volume and Issue: 74, P. 80 - 87

Published: Feb. 1, 2022

Language: Английский

---

Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(8), P. 4258 - 4271

Published: April 14, 2022

Abstract The link between genomic structure and biological function is yet to be consolidated, it is, however, clear that physical manipulation of the genome, driven by activity a variety proteins, crucial step. To understand consequences forces underlying genome organization, we build coarse-grained polymer model featuring three fundamentally distinct classes interactions: lengthwise compaction, i.e., compaction chromosomes along its contour, self-adhesion among epigenetically similar segments, adhesion chromosome segments nuclear envelope or lamina. We postulate these types interactions sufficiently represent concerted action different proteins organizing architecture show an interplay can recapitulate architectural variants observed across tree life. elucidates how arising from drive drastic, predictable, changes in global architecture, makes testable predictions. posit precise control over vivo key regulation architecture.

Language: Английский

---

Chromatin reprogramming and bone regeneration in vitro and in vivo via the microtopography-induced constriction of cell nuclei

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: 7(11), P. 1514 - 1529

Published: June 12, 2023

Language: Английский

---

Behind the scenes: How RNA orchestrates the epigenetic regulation of gene expression

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 25, 2023

Non-coding DNA accounts for approximately 98.5% of the human genome. Once labeled as “junk DNA”, this portion genome has undergone a progressive re-evaluation and it is now clear that some its transcriptional products, belonging to non-coding RNAs (ncRNAs), are key players in cell regulatory networks. A growing body evidence demonstrates crucial impact ncRNAs on mammalian gene expression. Here, we focus defined relationship between chromatin-interacting RNAs, particularly long RNA (lncRNA), enhancer (eRNA), natural antisense transcript (ncNAT), circular (circRNA) epigenome, common ground where both protein species converge regulate cellular functions. Through several examples, review provides an overview variety targets, interactors, mechanisms involved RNA-mediated modulation loci-specific epigenetic states, fundamental evolutive strategy orchestrate expression timely reversible manner. We will discuss how regulation impacts development tissue homeostasis alteration contributes onset progression many different diseases, cancer.

Language: Английский

---

Dynamic 3D genome reorganization during senescence: defining cell states through chromatin

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 18, 2023

Abstract Cellular senescence, a cell state characterized by growth arrest and insensitivity to stimulatory hormones, is accompanied massive change in chromatin organization. Senescence can be induced range of physiological signals pathological stresses was originally thought an irreversible state, implicated normal development, wound healing, tumor suppression aging. Recently cellular senescence shown reversible some cases, with exit being triggered the modulation cell’s transcriptional program four Yamanaka factors, p53 or H3K9me3, PDK1, and/or depletion AP-1. Coincident reversal are changes organization, most notably loss senescence-associated heterochromatin foci (SAHF) found oncogene-induced senescence. In addition fixed-cell imaging, conformation capture multi-omics have been used examine reorganization at different spatial resolutions during They identify determinants SAHF formation other key features that differentiate distinct types Not surprisingly, multiple including time induction, type stress experienced, involved, influence global Here we discuss how three-dimensional organization genome contribute regulation transcription stages particular, contributions heterochromatin- lamina-mediated interactions, gene expression, control mechanisms discussed. We propose high-resolution temporal analyses landscape will early markers states help guide clinical diagnosis.

Language: Английский

---

Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 22, 2024

B-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous using Auxin-inducible degron technology.

Language: Английский

---