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Glia Aug 2020Oligodendrocytes, the myelinating cells in the vertebrate central nervous system, produce myelin sheaths to enable saltatory propagation of action potentials. The... (Review)
Review
Oligodendrocytes, the myelinating cells in the vertebrate central nervous system, produce myelin sheaths to enable saltatory propagation of action potentials. The process of oligodendrocyte myelination entails a stepwise progression from precursor specification to differentiation, which is coordinated by a series of transcriptional and chromatin remodeling events. ATP-dependent chromatin remodeling enzymes, which utilize ATP as an energy source to control chromatin dynamics and regulate the accessibility of chromatin to transcriptional regulators, are critical for oligodendrocyte lineage development and regeneration. In this review, we focus on the latest insights into the spatial and temporal specificity of chromatin remodelers during oligodendrocyte development, myelinogenesis, and regeneration. We will also bring together various plausible mechanisms by which lineage specific transcriptional regulators coordinate with chromatin remodeling factors for programming genomic landscapes to specifically modulate these different processes during developmental myelination and remyelination upon injury.
Topics: Animals; Cell Differentiation; Central Nervous System; Chromatin Assembly and Disassembly; Humans; Myelin Sheath; Oligodendroglia; Remyelination
PubMed: 32460418
DOI: 10.1002/glia.23837 -
Genes Mar 2021ADP-ribosylation, is a reversible post-translational modification implicated in major biological functions. Poly ADP-ribose polymerases (PARP) are specialized enzymes... (Review)
Review
ADP-ribosylation, is a reversible post-translational modification implicated in major biological functions. Poly ADP-ribose polymerases (PARP) are specialized enzymes that catalyze the addition of ADP ribose units from "nicotinamide adenine dinucleotide-donor molecules" to their target substrates. This reaction known as PARylation modulates essential cellular processes including DNA damage response, chromatin remodeling, DNA methylation and gene expression. Herein, we discuss emerging roles of PARP1 in chromatin remodeling and epigenetic regulation, focusing on its therapeutic implications for cancer treatment and beyond.
Topics: Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Humans; Neoplasms; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Protein Processing, Post-Translational
PubMed: 33804735
DOI: 10.3390/genes12030446 -
Seminars in Cancer Biology Sep 2022Epigenetic patterns in a cell control the expression of genes and consequently determine the phenotype of a cell. Cancer cells possess altered epigenomes which include... (Review)
Review
Epigenetic patterns in a cell control the expression of genes and consequently determine the phenotype of a cell. Cancer cells possess altered epigenomes which include aberrant patterns of DNA methylation, histone tail modifications, nucleosome positioning and of the three-dimensional chromatin organization within a nucleus. These altered epigenetic patterns are potential useful biomarkers to detect cancer cells and to classify tumor types. In addition, the cancer epigenome dictates the response of a cancer cell to therapeutic intervention and, therefore its knowledge, will allow to predict response to different therapeutic approaches. Here we review the current state-of-the-art technologies that have been developed to decipher epigenetic patterns on the genomic level and discuss how these methods are potentially useful for precision oncology.
Topics: Chromatin Assembly and Disassembly; DNA Methylation; Epigenomics; Humans; Neoplasms; Precision Medicine
PubMed: 32822861
DOI: 10.1016/j.semcancer.2020.08.004 -
Journal of Molecular Biology Mar 2021Gene regulation programs establish cellular identity and rely on dynamic changes in the structural packaging of genomic DNA. The DNA is packaged in chromatin, which is... (Review)
Review
Gene regulation programs establish cellular identity and rely on dynamic changes in the structural packaging of genomic DNA. The DNA is packaged in chromatin, which is formed from arrays of nucleosomes displaying different degree of compaction and different lengths of inter-nucleosomal linker DNA. The nucleosome represents the repetitive unit of chromatin and is formed by wrapping 145-147 basepairs of DNA around an octamer of histone proteins. Each of the four histones is present twice and has a structured core and intrinsically disordered terminal tails. Chromatin dynamics are triggered by inter- and intra-nucleosome motions that are controlled by the DNA sequence, the interactions between the histone core and the DNA, and the conformations, positions, and DNA interactions of the histone tails. Understanding chromatin dynamics requires studying all these features at the highest possible resolution. For this, molecular dynamics simulations can be used as a powerful complement or alternative to experimental approaches, from which it is often very challenging to characterize the structural features and atomic interactions controlling nucleosome motions. Molecular dynamics simulations can be performed at different resolutions, by coarse graining the molecular system with varying levels of details. Here we review the successes and the remaining challenges of the application of atomic resolution simulations to study the structure and dynamics of nucleosomes and their complexes with interacting partners.
Topics: Acetylation; Chromatin Assembly and Disassembly; DNA; Histones; Methylation; Molecular Dynamics Simulation; Nucleic Acid Conformation; Nucleosomes; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Processing, Post-Translational
PubMed: 33309853
DOI: 10.1016/j.jmb.2020.166744 -
DNA Repair Dec 2021Unlike all other biological molecules that are degraded and replaced if damaged, DNA must be repaired as chromosomes cannot be replaced. Indeed, DNA endures a wide... (Review)
Review
Unlike all other biological molecules that are degraded and replaced if damaged, DNA must be repaired as chromosomes cannot be replaced. Indeed, DNA endures a wide variety of structural damage that need to be repaired accurately to maintain genomic stability and proper functioning of cells and to prevent mutation leading to disease. Given that the genome is packaged into chromatin within eukaryotic cells, it has become increasingly evident that the chromatin context of DNA both facilitates and regulates DNA repair processes. In this review, we discuss mechanisms involved in removal of histones (chromatin disassembly) from around DNA lesions, by histone chaperones and chromatin remodelers, that promotes accessibility of the DNA repair machinery. We also elaborate on how the deposition of core histones and specific histone variants onto DNA (chromatin assembly) during DNA repair promotes repair processes, the role of histone post translational modifications in these processes and how chromatin structure is reestablished after DNA repair is complete.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; DNA Repair; Histones; Humans
PubMed: 34687987
DOI: 10.1016/j.dnarep.2021.103240 -
ELife Mar 2024To find nucleosomes, chromatin remodelers slide and hop along DNA, and their direction of approach affects the direction that nucleosomes slide in.
To find nucleosomes, chromatin remodelers slide and hop along DNA, and their direction of approach affects the direction that nucleosomes slide in.
Topics: Nucleosomes; DNA-Binding Proteins; Saccharomyces cerevisiae Proteins; Chromatin Assembly and Disassembly; Chromatin
PubMed: 38488335
DOI: 10.7554/eLife.96836 -
Current Opinion in Structural Biology Jun 2023Heterochromatin formation has been proposed to involve phase transitions on the level of the three-dimensional folding of heterochromatin regions and the liquid-liquid... (Review)
Review
Heterochromatin formation has been proposed to involve phase transitions on the level of the three-dimensional folding of heterochromatin regions and the liquid-liquid demixing of heterochromatin proteins. Here, I outline the hallmarks of such transitions and the current challenges to detect them in living cells. I further discuss the abundance and properties of prominent heterochromatin proteins and relate them to their potential role in driving phase transitions. Recent data from mouse fibroblasts indicate that pericentric heterochromatin is organized via a reordering transition on the level of heterochromatin regions that does not necessarily involve liquid-liquid demixing of heterochromatin proteins. Evaluating key hallmarks of the different candidate phase transition mechanisms across cell types and species will be needed to complete the current picture.
Topics: Animals; Mice; Heterochromatin; Chromatin Assembly and Disassembly
PubMed: 37087823
DOI: 10.1016/j.sbi.2023.102597 -
Cells Feb 2023During transcription, DNA replication and repair, chromatin structure is constantly modified to reveal specific genetic regions and allow access to DNA-interacting... (Review)
Review
During transcription, DNA replication and repair, chromatin structure is constantly modified to reveal specific genetic regions and allow access to DNA-interacting enzymes. ATP-dependent chromatin remodelling complexes use the energy of ATP hydrolysis to modify chromatin architecture by repositioning and rearranging nucleosomes. These complexes are defined by a conserved SNF2-like, catalytic ATPase subunit and are divided into four families: CHD, SWI/SNF, ISWI and INO80. ATP-dependent chromatin remodellers are crucial in regulating development and stem cell biology in numerous organs, including the inner ear. In addition, mutations in genes coding for proteins that are part of chromatin remodellers have been implicated in numerous cases of neurosensory deafness. In this review, we describe the composition, structure and functional activity of these complexes and discuss how they contribute to hearing and neurosensory deafness.
Topics: Humans; Chromatin; Transcription Factors; Chromatin Assembly and Disassembly; Adenosine Triphosphate; Hearing Loss, Sensorineural
PubMed: 36831199
DOI: 10.3390/cells12040532 -
Neurobiology of Learning and Memory May 2021Epigenetic mechanisms have recently emerged as critical regulators of brain function in health and disease. By controlling the accessibility and the expression of... (Review)
Review
Epigenetic mechanisms have recently emerged as critical regulators of brain function in health and disease. By controlling the accessibility and the expression of specific genes, these pathways can mediate transient and long-lasting changes in neuronal function in both physiological and pathological contexts. Due to the extreme complexity of the epigenetic regulatory landscape, emerging methods that directly assay chromatin accessibility are of particular interest. Here, I review recent insights gained on open and closed chromatin states in the brain, with emphasis on neuropsychiatric disorders. These advances generated an invaluable wealth of information that can help us better understand gene regulation in the brain and its impairments that contribute to the development of disease.
Topics: Brain; Chromatin; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Gene Expression Regulation; Humans; Mental Disorders
PubMed: 33845131
DOI: 10.1016/j.nlm.2021.107438 -
Cancer Metastasis Reviews Jun 2023The ATP-dependent chromatin remodeling complex SWI/SNF (also called BAF) is critical for the regulation of gene expression. During the evolution from yeast to mammals,... (Review)
Review
The ATP-dependent chromatin remodeling complex SWI/SNF (also called BAF) is critical for the regulation of gene expression. During the evolution from yeast to mammals, the BAF complex has evolved an enormous complexity that contains a high number of subunits encoded by various genes. Emerging studies highlight the frequent involvement of altered mammalian SWI/SNF chromatin-remodeling complexes in human cancers. Here, we discuss the recent advances in determining the structure of SWI/SNF complexes, highlight the mechanisms by which mutations affecting these complexes promote cancer, and describe the promising emerging opportunities for targeted therapies.
Topics: Animals; Humans; Transcription Factors; Neoplasms; Mutation; Chromatin Assembly and Disassembly; Mammals
PubMed: 37093326
DOI: 10.1007/s10555-023-10102-5