scholarly journals Histone Modifications and Other Facets of Epigenetic Regulation in Trypanosomatids: Leaving Their Mark

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Swati Saha
Keyword(s):  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Posttranslational Modifications ◽  
High Resolution Mass Spectrometry ◽  
Three Dimensional ◽  
Early Years ◽  
Host Immune System ◽  
3D Genome ◽  
Cellular Processes ◽  
The Impact

ABSTRACT Histone posttranslational modifications (PTMs) modulate several eukaryotic cellular processes, including transcription, replication, and repair. Vast arrays of modifications have been identified in conventional eukaryotes over the last 20 to 25 years. While initial studies uncovered these primarily on histone tails, multiple modifications were subsequently found on the central globular domains as well. Histones are evolutionarily conserved across eukaryotes, and a large number of their PTMs and the functional relevance of these PTMs are largely conserved. Trypanosomatids, however, are early diverging eukaryotes. Although possessing all four canonical histones as well as several variants, their sequences diverge from those of other eukaryotes, particularly in the tails. Consequently, the modifications they carry also vary. Initial analyses almost 15 years ago suggested that trypanosomatids possessed a smaller collection of histone modifications. However, exhaustive high resolution mass spectrometry analyses in the last few years have overturned this belief, and it is now evident that the “histone code” proposed by Allis and coworkers in the early years of this century is as complex in these organisms as in other eukaryotes. Trypanosomatids cause several diseases, and the members of this group of organisms have varied lifestyles, evolving diverse mechanisms to evade the host immune system, some of which have been found to be principally controlled by epigenetic mechanisms. This minireview aims to acquaint the reader with the impact of histone PTMs on trypanosomatid cellular processes, as well as other facets of trypanosomatid epigenetic regulation, including the influence of three-dimensional (3D) genome architecture, and discusses avenues for future investigations.

scholarly journals 3DIV update for 2021: a comprehensive resource of 3D genome and 3D cancer genome

2020 ◽  
Vol 49 (D1) ◽  
pp. D38-D46
Author(s):  
Kyukwang Kim ◽  
Insu Jang ◽  
Mooyoung Kim ◽  
Jinhyuk Choi ◽  
Min-Seo Kim ◽  
...  
Keyword(s):  
Cell Line ◽  
Large Scale ◽  
Three Dimensional ◽  
Cancer Cell Line ◽  
Cancer Genome ◽  
Structural Variations ◽  
3D Genome ◽  
Tightly Coupled ◽  
Regulatory Effects ◽  
The Impact

Abstract Three-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due to the lack of appropriate tools specialized for disorganized higher-order chromatin structure. Here, we updated a 3D-genome Interaction Viewer and database named 3DIV by uniformly processing ∼230 billion raw Hi-C reads to expand our contents to the 3D cancer genome. The updates of 3DIV are listed as follows: (i) the collection of 401 samples including 220 cancer cell line/tumor Hi-C data, 153 normal cell line/tissue Hi-C data, and 28 promoter capture Hi-C data, (ii) the live interactive manipulation of the 3D cancer genome to simulate the impact of structural variations and (iii) the reconstruction of Hi-C contact maps by user-defined chromosome order to investigate the 3D genome of the complex genomic rearrangement. In summary, the updated 3DIV will be the most comprehensive resource to explore the gene regulatory effects of both the normal and cancer 3D genome. ‘3DIV’ is freely available at http://3div.kr.

scholarly journals Cohesin Mutations in Cancer: Emerging Therapeutic Targets

2021 ◽  
Vol 22 (13) ◽  
pp. 6788
Author(s):  
Jisha Antony ◽  
Chue Vin Chin ◽  
Julia A. Horsfield
Keyword(s):  
Therapeutic Potential ◽  
Three Dimensional ◽  
Neoplastic Transformation ◽  
Pharmacological Agents ◽  
Functional Studies ◽  
Cellular Processes ◽  
Chromatid Cohesion ◽  
Key Events ◽  
The Impact ◽  
Mutant Cells

The cohesin complex is crucial for mediating sister chromatid cohesion and for hierarchal three-dimensional organization of the genome. Mutations in cohesin genes are present in a range of cancers. Extensive research over the last few years has shown that cohesin mutations are key events that contribute to neoplastic transformation. Cohesin is involved in a range of cellular processes; therefore, the impact of cohesin mutations in cancer is complex and can be cell context dependent. Candidate targets with therapeutic potential in cohesin mutant cells are emerging from functional studies. Here, we review emerging targets and pharmacological agents that have therapeutic potential in cohesin mutant cells.

scholarly journals Biology of Chromatin

2021 ◽  
pp. 1-28
Author(s):  
Renato Paro ◽  
Ueli Grossniklaus ◽  
Raffaella Santoro ◽  
Anton Wutz
Keyword(s):  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Posttranslational Modifications ◽  
Gene Promoters ◽  
Histone H2a ◽  
Histone Proteins ◽  
3 Dimensional ◽  
Telomere Function ◽  
Dna Replication And Repair ◽  
Nucleosomal Structure

AbstractThis chapter provides an introduction to chromatin. We will examine the organization of the genome into a nucleosomal structure. DNA is wrapped around a globular complex of 8 core histone proteins, two of each histone H2A, H2B, H3, and H4. This nucleosomal arrangement is the context in which information can be established along the sequence of the DNA for regulating different aspects of the chromosome, including transcription, DNA replication and repair processes, recombination, kinetochore function, and telomere function. Posttranslational modifications of histone proteins and modifications of DNA bases underlie chromatin-based epigenetic regulation. Enzymes that catalyze histone modifications are considered writers. Conceptually, erasers remove these modifications, and readers are proteins binding these modifications and can target specific functions. On a larger scale, the 3-dimensional (3D) organization of chromatin in the nucleus also contributes to gene regulation. Whereas chromosomes are condensed during mitosis and segregated during cell division, they occupy discrete volumes called chromosome territories during interphase. Looping or folding of DNA can bring regulatory elements including enhancers close to gene promoters. Recent techniques facilitate understanding of 3D contacts at high resolution. Lastly, chromatin is dynamic and changes in histone occupancy, histone modifications, and accessibility of DNA contribute to epigenetic regulation.

scholarly journals Rice 3D chromatin structure correlates with sequence variation and meiotic recombination rate

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Agnieszka A. Golicz ◽  
Prem L. Bhalla ◽  
David Edwards ◽  
Mohan B. Singh
Keyword(s):  
Meiotic Recombination ◽  
Recombination Rate ◽  
Sequence Variation ◽  
Genome Structure ◽  
Rice Genome ◽  
Three Dimensional ◽  
3D Genome ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
Topologically Associated Domains

AbstractGenomes of many eukaryotic species have a defined three-dimensional architecture critical for cellular processes. They are partitioned into topologically associated domains (TADs), defined as regions of high chromatin inter-connectivity. While TADs are not a prominent feature of A. thaliana genome organization, they have been reported for other plants including rice, maize, tomato and cotton and for which TAD formation appears to be linked to transcription and chromatin epigenetic status. Here we show that in the rice genome, sequence variation and meiotic recombination rate correlate with the 3D genome structure. TADs display increased SNP and SV density and higher recombination rate compared to inter-TAD regions. We associate the observed differences with the TAD epigenetic landscape, TE composition and an increased incidence of meiotic crossovers.

scholarly journals Hi–C interaction graph analysis reveals the impact of histone modifications in chromatin shape

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Emre Sefer
Keyword(s):  
Histone Modifications ◽  
Spatial Organization ◽  
Three Dimensional ◽  
Cell Types ◽  
Interaction Graph ◽  
Chromosome Conformation ◽  
A Genome ◽  
Topologically Associated Domains ◽  
Wide Scale ◽  
The Impact

AbstractChromosome conformation capture experiments such as Hi–C map the three-dimensional spatial organization of genomes in a genome-wide scale. Even though Hi–C interactions are not biased towards any of the histone modifications, previous analysis has revealed denser interactions around many histone modifications. Nevertheless, simultaneous effects of these modifications in Hi–C interaction graph have not been fully characterized yet, limiting our understanding of genome shape. Here, we propose ChromatinCoverage and its extension TemporalPrizeCoverage methods to decompose Hi–C interaction graph in terms of known histone modifications. Both methods are based on set multicover with pairs, where each Hi–C interaction is tried to be covered by histone modification pairs. We find 4 histone modifications H3K4me1, H3K4me3, H3K9me3, H3K27ac to be significantly predictive of most Hi–C interactions across species, cell types and cell cycles. The proposed methods are quite effective in predicting Hi–C interactions and topologically-associated domains in one species, given it is trained on another species or cell types. Overall, our findings reveal the impact of subset of histone modifications in chromatin shape via Hi–C interaction graph.

scholarly journals Encounters in Three Dimensions: How Nuclear Topology Shapes Genome Integrity

2021 ◽  
Vol 12 ◽  
Author(s):  
Robin Sebastian ◽  
Mirit I. Aladjem ◽  
Philipp Oberdoerffer
Keyword(s):  
Dna Repair ◽  
Genome Instability ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Histone H2ax ◽  
3D Genome ◽  
New Findings ◽  
Topologically Associated Domains ◽  
Organizational Features ◽  
The Impact

Almost 25 years ago, the phosphorylation of a chromatin component, histone H2AX, was discovered as an integral part of the DNA damage response in eukaryotes. Much has been learned since then about the control of DNA repair in the context of chromatin. Recent technical and computational advances in imaging, biophysics and deep sequencing have led to unprecedented insight into nuclear organization, highlighting the impact of three-dimensional (3D) chromatin structure and nuclear topology on DNA repair. In this review, we will describe how DNA repair processes have adjusted to and in many cases adopted these organizational features to ensure accurate lesion repair. We focus on new findings that highlight the importance of chromatin context, topologically associated domains, phase separation and DNA break mobility for the establishment of repair-conducive nuclear environments. Finally, we address the consequences of aberrant 3D genome maintenance for genome instability and disease.

scholarly journals The Histone Modifications of Neuronal Plasticity

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Huixia Geng ◽  
Hongyang Chen ◽  
Haiying Wang ◽  
Lai Wang
Keyword(s):  
Gene Expression ◽  
Learning And Memory ◽  
Histone Modifications ◽  
Posttranslational Modifications ◽  
Synapse Formation ◽  
Environmental Changes ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Dynamic Synapse ◽  
Histone Codes

Nucleosomes composed of histone octamer and DNA are the basic structural unit in the eukaryote chromosome. Under the stimulation of various factors, histones will undergo posttranslational modifications such as methylation, phosphorylation, acetylation, and ubiquitination, which change the three-dimensional structure of chromosomes and affect gene expression. Therefore, the combination of different states of histone modifications modulates gene expression is called histone code. The formation of learning and memory is one of the most important mechanisms for animals to adapt to environmental changes. A large number of studies have shown that histone codes are involved in the formation and consolidation of learning and memory. Here, we review the most recent literature of histone modification in regulating neurogenesis, dendritic spine dynamic, synapse formation, and synaptic plasticity.

scholarly journals A Tale of Two States: Pluripotency Regulation of Telomeres

2021 ◽  
Vol 9 ◽  
Author(s):  
Clara Lopes Novo
Keyword(s):  
Phase Separation ◽  
Genome Stability ◽  
Chromosome Instability ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
3D Genome ◽  
Cellular Processes ◽  
Damage Repair ◽  
Dimensional Network ◽  
Telomere Regulation

Inside the nucleus, chromatin is functionally organized and maintained as a complex three-dimensional network of structures with different accessibility such as compartments, lamina associated domains, and membraneless bodies. Chromatin is epigenetically and transcriptionally regulated by an intricate and dynamic interplay of molecular processes to ensure genome stability. Phase separation, a process that involves the spontaneous organization of a solution into separate phases, has been proposed as a mechanism for the timely coordination of several cellular processes, including replication, transcription and DNA repair. Telomeres, the repetitive structures at the end of chromosomes, are epigenetically maintained in a repressed heterochromatic state that prevents their recognition as double-strand breaks (DSB), avoiding DNA damage repair and ensuring cell proliferation. In pluripotent embryonic stem cells, telomeres adopt a non-canonical, relaxed epigenetic state, which is characterized by a low density of histone methylation and expression of telomere non-coding transcripts (TERRA). Intriguingly, this telomere non-canonical conformation is usually associated with chromosome instability and aneuploidy in somatic cells, raising the question of how genome stability is maintained in a pluripotent background. In this review, we will explore how emerging technological and conceptual developments in 3D genome architecture can provide novel mechanistic perspectives for the pluripotent epigenetic paradox at telomeres. In particular, as RNA drives the formation of LLPS, we will consider how pluripotency-associated high levels of TERRA could drive and coordinate phase separation of several nuclear processes to ensure genome stability. These conceptual advances will provide a better understanding of telomere regulation and genome stability within the highly dynamic pluripotent background.

scholarly journals A deep learning approach to predict the impact of non-coding sequence variants on 3D chromatin structure

2019 ◽  
Author(s):  
Tuan Trieu ◽  
Ekta Khurana
Keyword(s):  
Deep Learning ◽  
Three Dimensional ◽  
Driver Gene ◽  
Driver Genes ◽  
Cancer Driver ◽  
3D Genome ◽  
Expression Of Genes ◽  
Coding Variants ◽  
The Impact ◽  
Multiple Patients

Three-dimensional structures of the genome play an important role in regulating the expression of genes. Non-coding variants have been shown to alter 3D genome structures to activate oncogenes in cancer. However, there is currently no method to predict the effect of DNA variants on 3D structures. We propose a deep learning method, DeepMILO, to learn DNA sequence features of CTCF/cohesin-mediated loops and to predict the effect of variants on these loops. DeepMILO consists of a convolutional and a recurrent neural network, and it can learn features beyond the presence of CTCF motifs and their orientations. Application of DeepMILO on a cohort of 241 malignant lymphoma patients with whole-genome sequences revealed CTCF/cohesin-mediated loops disrupted in multiple patients. These disrupted loops contain known cancer driver genes and novel genes. Our results show mutations at loop boundaries are associated with upregulation of the cancer driver gene BCL2 and may point to a possible new mechanism for its dysregulation via alteration of 3D loop structures.

Analyzing the Impact of X-Ray Tomography on the Reliability of Integrated Circuits

2015 ◽  
Author(s):  
Halit Dogan ◽  
Md Mahbub Alam ◽  
Navid Asadizanjani ◽  
Sina Shahbazmohamadi ◽  
Domenic Forte ◽  
...  
Keyword(s):  
Integrated Circuits ◽  
Integrated Circuit ◽  
3D Imaging ◽  
Three Dimensional ◽  
Serial Sectioning ◽  
Promising Technique ◽  
Flash Memories ◽  
X Ray ◽  
3D Information ◽  
The Impact

Abstract X-ray tomography is a promising technique that can provide micron level, internal structure, and three dimensional (3D) information of an integrated circuit (IC) component without the need for serial sectioning or decapsulation. This is especially useful for counterfeit IC detection as demonstrated by recent work. Although the components remain physically intact during tomography, the effect of radiation on the electrical functionality is not yet fully investigated. In this paper we analyze the impact of X-ray tomography on the reliability of ICs with different fabrication technologies. We perform a 3D imaging using an advanced X-ray machine on Intel flash memories, Macronix flash memories, Xilinx Spartan 3 and Spartan 6 FPGAs. Electrical functionalities are then tested in a systematic procedure after each round of tomography to estimate the impact of X-ray on Flash erase time, read margin, and program operation, and the frequencies of ring oscillators in the FPGAs. A major finding is that erase times for flash memories of older technology are significantly degraded when exposed to tomography, eventually resulting in failure. However, the flash and Xilinx FPGAs of newer technologies seem less sensitive to tomography, as only minor degradations are observed. Further, we did not identify permanent failures for any chips in the time needed to perform tomography for counterfeit detection (approximately 2 hours).

Sign in / Sign up

Export Citation Format

Share Document