scholarly journals Chromatin Dynamics

2021 ◽  
pp. 29-47
Author(s):  
Renato Paro ◽  
Ueli Grossniklaus ◽  
Raffaella Santoro ◽  
Anton Wutz
Keyword(s):  
Dna Sequences ◽  
Eukaryotic Cell ◽  
Sequence Information ◽  
Chromatin Dynamics ◽  
Chromatin Template ◽  
Chromatin Remodeling Complexes ◽  
Molecular Machinery ◽  
Cell Type Specific ◽  
Nucleosomal Structure ◽  
The Stability

AbstractThe nucleus of a eukaryotic cell is a very busy place. Not only during replication of the DNA, but at any time in the cell cycle specific enzymes need access to genetic information to process reactions such as transcription and DNA repair. Yet, the nucleosomal structure of chromatin is primarily inhibitory to these processes and needs to be resolved in a highly orchestrated manner to allow developmental, organismal, and cell type-specific nuclear activities. This chapter explains how nucleosomes organize and structure the genome by interacting with specific DNA sequences. Variants of canonical histones can change the stability of the nucleosomal structure and also provide additional epigenetic layers of information. Chromatin remodeling complexes work locally to alter the regular beads-on-a-string organization and provide access to transcription and other DNA processing factors. Conversely, factors like histone chaperones and highly precise templating and copying mechanisms are required for the reassembly of nucleosomes and reestablishment of the epigenetic landscape after passage of activities processing DNA sequence information. A very intricate molecular machinery ensures a highly dynamic yet heritable chromatin template.

scholarly journals And yet, it moves: nuclear and chromatin dynamics of a heterochromatic double-strand break

2017 ◽  
Vol 372 (1731) ◽  
pp. 20160291 ◽  
Author(s):  
P. Christopher Caridi ◽  
Laetitia Delabaere ◽  
Grzegorz Zapotoczny ◽  
Irene Chiolo
Keyword(s):  
Dna Sequences ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Nuclear Periphery ◽  
Strand Break ◽  
Double Strand Break ◽  
Chromatin Dynamics ◽  
Recombination Repair ◽  
The Stability

Heterochromatin is mostly composed of repeated DNA sequences prone to aberrant recombination. How cells maintain the stability of these sequences during double-strand break (DSB) repair has been a long-standing mystery. Studies in Drosophila cells revealed that faithful homologous recombination repair of heterochromatic DSBs relies on the striking relocalization of repair sites to the nuclear periphery before Rad51 recruitment and repair progression. Here, we summarize our current understanding of this response, including the molecular mechanisms involved, and conserved pathways in mammalian cells. We will highlight important similarities with pathways identified in budding yeast for repair of other types of repeated sequences, including rDNA and short telomeres. We will also discuss the emerging role of chromatin composition and regulation in heterochromatin repair progression. Together, these discoveries challenged previous assumptions that repair sites are substantially static in multicellular eukaryotes, that heterochromatin is largely inert in the presence of DSBs, and that silencing and compaction in this domain are obstacles to repair. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

scholarly journals Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 4034-4046 ◽  
Author(s):  
Giuseppe Zardo ◽  
Alberto Ciolfi ◽  
Laura Vian ◽  
Linda M. Starnes ◽  
Monia Billi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcriptional Control ◽  
Transcriptional Level ◽  
Seed Region ◽  
Mrna Targets ◽  
Epigenetic Events ◽  
Evolutionarily Conserved ◽  
Lineage Decision ◽  
Chromatin Remodeling Complexes

Abstract Epigenetic modifications regulate developmental genes involved in stem cell identity and lineage choice. NFI-A is a posttranscriptional microRNA-223 (miR-223) target directing human hematopoietic progenitor lineage decision: NFI-A induction or silencing boosts erythropoiesis or granulopoiesis, respectively. Here we show that NFI-A promoter silencing, which allows granulopoiesis, is guaranteed by epigenetic events, including the resolution of opposing chromatin “bivalent domains,” hypermethylation, recruitment of polycomb (PcG)–RNAi complexes, and miR-223 promoter targeting activity. During granulopoiesis, miR-223 localizes inside the nucleus and targets the NFI-A promoter region containing PcGs binding sites and miR-223 complementary DNA sequences, evolutionarily conserved in mammalians. Remarkably, both the integrity of the PcGs-RNAi complex and DNA sequences matching the seed region of miR-223 are required to induce NFI-A transcriptional silencing. Moreover, ectopic miR-223 expression in human myeloid progenitors causes heterochromatic repression of NFI-A gene and channels granulopoiesis, whereas its stable knockdown produces the opposite effects. Our findings indicate that, besides the regulation of translation of mRNA targets, endogenous miRs can affect gene expression at the transcriptional level, functioning in a critical interface between chromatin remodeling complexes and the genome to direct fate lineage determination of hematopoietic progenitors.

scholarly journals Making of fusion genes in cancer: An in-silico study of mechanism of chromosomal translocations

2018 ◽  
Author(s):  
Kiran Lalwani ◽  
Shivani Sheth ◽  
Inayatullah Sheikh ◽  
Afzal Ansari ◽  
Fulesh Kunwar ◽  
...  
Keyword(s):  
Dna Sequences ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Fusion Gene ◽  
Genetic Material ◽  
Chromosomal Translocations ◽  
In Silico Study ◽  
Clinical Consequences ◽  
The Stability ◽  
Genomic Regions

Chromosomal translocations involve exchange of genetic material between non- homologous chromosomes leading to the formation of a fusion gene with altered function. The clinical consequences of non-random and recurrent chromosomal translocations have been so well understood in carcinogenesis that they serve as diagnostic and prognostic markers and also help in therapy decisions, mainly in leukemia and lymphoma. However, the molecular mechanisms underlying these recurrent genetic exchanges are yet to be understood. Various approaches employed include the extent of the vicinity of the partner chromosomes in the nucleus, DNA sequences at the breakpoints, etc. The present study addresses the stability of DNA sequences at the breakpoint regions using in-silico approach in terms of physicochemical properties such as; AT%, flexibility, melting temperature, enthalpy, entropy, stacking energy and free energy. Changes in these properties may lead to instability of DNA which could affect gene expression in particular and genome organization in general. Our study indicates that the fusion sequences are comparatively more unstable and hence, more prone to breakage. Current study along with others could lead to developing a model for predicting breakage prone genomic regions using this novel in-silico approach.

scholarly journals SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models

2020 ◽  
Author(s):  
Yupeng Wang ◽  
Rosario B. Jaime-Lara ◽  
Abhrarup Roy ◽  
Ying Sun ◽  
Xinyue Liu ◽  
...  
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Dna Sequences ◽  
Cell Types ◽  
Learning Models ◽  
Cell Type ◽  
Coding Sequences ◽  
Sequence Features ◽  
Cell Type Specific ◽  
Different Cell Types

AbstractWe propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of “strong enhancer” chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, sequential k-mer (k=5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers including gkm-SVM and DanQ, with regard to distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL is able to directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified according to their sequence features. SeqEnhDL is publicly available at https://github.com/wyp1125/SeqEnhDL.

New insights into sequence variation in the IGS region of 21 cyathostomin species and the implication for molecular identification

Parasitology ◽  
2012 ◽  
Vol 139 (8) ◽  
pp. 1063-1073 ◽  
Author(s):  
K. CWIKLINSKI ◽  
F. N. J. KOOYMAN ◽  
D. C. K. VAN DOORN ◽  
J. B. MATTHEWS ◽  
J. E. HODGKINSON
Keyword(s):  
Comparative Analysis ◽  
Dna Sequences ◽  
Sequence Variation ◽  
Intergenic Spacer ◽  
Parasitic Nematodes ◽  
Sequence Information ◽  
Detailed Knowledge ◽  
Life Cycle Stages ◽  
Third Stage ◽  
Specific Variation

SUMMARYCyathostomins comprise a group of 50 species of parasitic nematodes that infect equids. Ribosomal DNA sequences, in particular the intergenic spacer (IGS) region, have been utilized via several methodologies to identify pre-parasitic stages of the commonest species that affect horses. These methods rely on the availability of accurate sequence information for each species, as well as detailed knowledge of the levels of intra- and inter-specific variation. Here, the IGS DNA region was amplified and sequenced from 10 cyathostomin species for which sequence was not previously available. Also, additional IGS DNA sequences were generated from individual worms of 8 species already studied. Comparative analysis of these sequences revealed a greater range of intra-specific variation than previously reported (up to 23%); whilst the level of inter-specific variation (3–62%) was similar to that identified in earlier studies. The reverse line blot (RLB) method has been used to exploit the cyathostomin IGS DNA region for species identification. Here, we report validation of novel and existing DNA probes for identification of cyathostomins using this method and highlight their application in differentiating life-cycle stages such as third-stage larvae that cannot be identified to species by morphological means†.

scholarly journals Chromatin-remodeling and the initiation of transcription

2015 ◽  
Vol 48 (4) ◽  
pp. 465-470 ◽  
Author(s):  
Yahli Lorch ◽  
Roger D. Kornberg
Keyword(s):  
Chromatin Remodeling ◽  
Dna Sequences ◽  
Initiation Of Transcription ◽  
Chromatin Remodeling Complexes ◽  
Promoter Dna

AbstractThe nucleosome serves as a general gene repressor by the occlusion of regulatory and promoter DNA sequences. Repression is relieved by the SWI/SNF-RSC family of chromatin-remodeling complexes. Research reviewed here has revealed the essential features of the remodeling process.

scholarly journals Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming

2020 ◽  
Vol 89 (1) ◽  
pp. 235-253 ◽  
Author(s):  
Mitzi I. Kuroda ◽  
Hyuckjoon Kang ◽  
Sandip De ◽  
Judith A. Kassis
Keyword(s):  
Transcription Factor ◽  
Histone Modifications ◽  
Dna Sequences ◽  
Normal Development ◽  
Polycomb Group ◽  
Cell Type ◽  
Trithorax Group ◽  
Cell Type Specific ◽  
Chromatin Proteins ◽  
Regulatory Potential

Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of the genome by chromatin proteins, histone modifications, and differential compaction is largely sufficient to reveal the locations of genes and their differential activity states. The Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are the central players in this cell type–specific chromatin organization. PcG function was originally viewed as being solely repressive and irreversible, as observed at the homeotic loci in flies and mammals. However, it is now clear that modular and reversible PcG function is essential at most developmental genes. Focusing mainly on recent advances, we review evidence for how PcG and TrxG patterns change dynamically during cell type transitions. The ability to implement cell type–specific transcriptional programming with exquisite fidelity is essential for normal development.

scholarly journals Heat Shock Cognate 70 Functions as A Chaperone for the Stability of Kinetochore Protein CENP-N in Holocentric Insect Silkworms

2019 ◽  
Vol 20 (23) ◽  
pp. 5823
Author(s):  
Bingqian Li ◽  
Zhiqing Li ◽  
Chenchen Lu ◽  
Li Chang ◽  
Dongchao Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Heat Shock ◽  
Dna Sequences ◽  
Cellular Localization ◽  
Control Cell ◽  
Protein A ◽  
Holocentric Chromosomes ◽  
Centromere Protein ◽  
Heat Shock Cognate 70 ◽  
The Stability

The centromere, in which kinetochore proteins are assembled, plays an important role in the accurate congression and segregation of chromosomes during cell mitosis. Although the function of the centromere and kinetochore is conserved from monocentric to holocentric, the DNA sequences of the centromere and components of the kinetochore are varied among different species. Given the lack of core centromere protein A (CENP-A) and CENP-C in the lepidopteran silkworm Bombyx mori, which possesses holocentric chromosomes, here we investigated the role of CENP-N, another important member of the centromere protein family essential for kinetochore assembly. For the first time, cellular localization and RNA interference against CENP-N have confirmed its kinetochore function in silkworms. To gain further insights into the regulation of CENP-N in the centromere, we analyzed the affinity-purified complex of CENP-N by mass spectrometry and identified 142 interacting proteins. Among these factors, we found that the chaperone protein heat shock cognate 70 (HSC70) is able to regulate the stability of CENP-N by prohibiting ubiquitin–proteasome pathway, indicating that HSC70 could control cell cycle-regulated degradation of CENP-N at centromeres. Altogether, the present work will provide a novel clue to understand the regulatory mechanism for the kinetochore activity of CENP-N during the cell cycle.

scholarly journals Inactivation of 14-3-3ς Influences Telomere Behavior and Ionizing Radiation-Induced Chromosomal Instability

2000 ◽  
Vol 20 (20) ◽  
pp. 7764-7772 ◽  
Author(s):  
Sonu Dhar ◽  
Jeremy A. Squire ◽  
M. Prakash Hande ◽  
Raymund J. Wellinger ◽  
Tej K. Pandita
Keyword(s):  
Dna Sequences ◽  
Nuclear Matrix ◽  
Mammalian Cells ◽  
Eukaryotic Cell ◽  
Checkpoint Control ◽  
Aberrant Chromosome ◽  
M Phase ◽  
Chromosomal Breaks ◽  
Radiation Induced

ABSTRACT Telomeres are complexes of repetitive DNA sequences and proteins constituting the ends of linear eukaryotic chromosomes. While these structures are thought to be associated with the nuclear matrix, they appear to be released from this matrix at the time when the cells exit from G2 and enter M phase. Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. The 14-3-3ς gene has been reported to be a checkpoint control gene, since it promotes G2 arrest following DNA damage. Here we demonstrate that inactivation of this gene influences genome integrity and cell survival. Analyses of chromosomes at metaphase showed frequent losses of telomeric repeat sequences, enhanced frequencies of chromosome end-to-end associations, and terminal nonreciprocal translocations in 14-3-3ς−/− cells. These phenotypes correlated with a reduction in the amount of G-strand overhangs at the telomeres and an altered nuclear matrix association of telomeres in these cells. Since the p53-mediated G1 checkpoint is operative in these cells, the chromosomal aberrations observed occurred preferentially in G2 after irradiation with gamma rays, corroborating the role of the 14-3-3ς protein in G2/M progression. The results also indicate that even in untreated cycling cells, occasional chromosomal breaks or telomere-telomere fusions trigger a G2 checkpoint arrest followed by repair of these aberrant chromosome structures before entering M phase. Since 14-3-3ς−/− cells are defective in maintaining G2 arrest, they enter M phase without repair of the aberrant chromosome structures and undergo cell death during mitosis. Thus, our studies provide evidence for the correlation among a dysfunctional G2/M checkpoint control, genomic instability, and loss of telomeres in mammalian cells.

scholarly journals Effect of Sequence-Directed Nucleosome Disruption on Cell-Type-Specific Repression by α2/Mcm1 in the Yeast Genome

2006 ◽  
Vol 5 (11) ◽  
pp. 1925-1933 ◽  
Author(s):  
Nobuyuki Morohashi ◽  
Yuichi Yamamoto ◽  
Shunsuke Kuwana ◽  
Wataru Morita ◽  
Heisaburo Shindo ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Nucleosome Positioning ◽  
Yeast Genome ◽  
Specific Gene ◽  
Cell Type ◽  
Chromatin Structural ◽  
A Cell ◽  
Cell Type Specific ◽  
Acting In Concert ◽  
Modest Effect

ABSTRACT In Saccharomyces cerevisiae, a-cell-specific genes are repressed in MATα cells by α2/Mcm1, acting in concert with the Ssn6-Tup1 corepressors and the Isw2 chromatin remodeling complex, and nucleosome positioning has been proposed as one mechanism of repression. However, prior studies showed that nucleosome positioning is not essential for repression by α2/Mcm1 in artificial reporter plasmids, and the importance of the nucleosome positioning remains questionable. We have tested the function of positioned nucleosomes through alteration of genomic chromatin at the a-cell-specific gene BAR1. We report here that a positioned nucleosome in the BAR1 promoter is disrupted in cis by the insertion of diverse DNA sequences such as poly(dA) · poly(dT) and poly(dC-dG) · poly(dC-dG), leading to inappropriate partial derepression of BAR1. Also, we show that isw2 mutation causes loss of nucleosome positioning in BAR1 in MATα cells as well as partial disruption of repression. Thus, nucleosome positioning is required for full repression, but loss of nucleosome positioning is not sufficient to relieve repression completely. Even though disruption of nucleosome positioning by the cis- and trans-acting modulators of chromatin has a modest effect on the level of transcription, it causes significant degradation of the α-mating pheromone in MATα cells, thereby affecting its cell type identity. Our results illustrate a useful paradigm for analysis of chromatin structural effects at genomic loci.

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