scholarly journals Genome-wide variability in recombination activity is associated with meiotic chromatin organization

2021 ◽  
pp. gr.275358.121
Author(s):  
Xiaofan Jin ◽  
Geoff Fudenberg ◽  
Katherine S Pollard
Keyword(s):  
Chromatin Organization ◽  
Recombination Activity ◽  
Genome Wide ◽  
Wide Variability

scholarly journals Genome-wide variability in recombination activity is associated with meiotic chromatin organization

2021 ◽  
Author(s):  
Xiaofan Jin ◽  
Geoff Fudenberg ◽  
Katherine S Pollard
Keyword(s):  
Meiotic Prophase ◽  
Three Dimensional ◽  
Strand Break ◽  
Early Prophase ◽  
Recombination Activity ◽  
Homologous Chromosomes ◽  
Genome Wide ◽  
Wide Variability ◽  
Genomic Regions ◽  
Negative Health Outcomes

Background: Recombination enables reciprocal exchange of genomic information between parental chromosomes and successful segregation of homologous chromosomes during meiosis. Errors in this process lead to negative health outcomes, while variability in recombination rate affects genome evolution. In mammals, most crossovers occur in hotspots defined by PRDM9 motifs, though PRDM9 binding sites are not all equally hot. We hypothesize that dynamic patterns of meiotic genome folding are linked to recombination activity. Results: We apply an integrative bioinformatics approach to analyze how three-dimensional (3D) chromosomal organization during meiosis relates to rates of double-strand-break (DSB) and crossover formation at PRDM9 hotspots. We show that active, spatially accessible genomic regions during meiotic prophase are associated with DSB-favoured hotspots, which further adopt a transient locally active configuration in early prophase. Conversely, crossover formation is depleted among DSBs in spatially accessible regions during meiotic prophase, particularly within gene bodies. We also find evidence that active chromatin regions have smaller average loop sizes in mammalian meiosis. Collectively, these findings establish that differences in chromatin architecture along chromosomal axes are associated with variable recombination activity. Conclusions: We propose an updated framework describing how 3D organization of brush-loop chromosomes during meiosis may modulate recombination.

scholarly journals The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilona E. Grabowicz ◽  
Bartek Wilczyński ◽  
Bożena Kamińska ◽  
Adria-Jaume Roura ◽  
Bartosz Wojtaś ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Genetic Alterations ◽  
Chromatin Organization ◽  
Open Chromatin ◽  
Low Grade ◽  
Strong Impact ◽  
Cell Matrix ◽  
Topologically Associating Domains ◽  
Genome Wide

AbstractGenome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we intersected genome-wide atlas data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in WHO low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found the set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing specific glioma-related genes. Moreover, many genes associated with the cell–matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by long-range contacts with enhancers. Presented results demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy.

scholarly journals Genome-wide transposon tagging reveals location-dependent effects on transcription and chromatin organization in Arabidopsis

2008 ◽  
Vol 55 (3) ◽  
pp. 514-525 ◽  
Author(s):  
Faye M. Rosin ◽  
Naohide Watanabe ◽  
Jean-Luc Cacas ◽  
Naohiro Kato ◽  
Juana M. Arroyo ◽  
...  
Keyword(s):  
Chromatin Organization ◽  
Transposon Tagging ◽  
Genome Wide

scholarly journals Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease

2012 ◽  
Vol 7 (1) ◽  
pp. 103 ◽  
Author(s):  
Raquel Ma Fernández ◽  
Marta Bleda ◽  
Rocío Núñez-Torres ◽  
Ignacio Medina ◽  
Berta Luzón-Toro ◽  
...  
Keyword(s):  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Network Analyses ◽  
Genome Wide ◽  
Wide Variability

scholarly journals Ubiquitylated H2A.Z nucleosomes are associated with nuclear architectural proteins and global transcriptional silencing

2019 ◽  
Author(s):  
Marlee K. Ng ◽  
Ulrich Braunschweig ◽  
Benjamin J. Blencowe ◽  
Peter Cheung
Keyword(s):  
Gene Silencing ◽  
Transcriptional Repression ◽  
Transcriptional Silencing ◽  
Higher Order ◽  
Chromatin Organization ◽  
Post Translational Modification ◽  
H3k4 Methylation ◽  
Genome Wide ◽  
Architectural Proteins ◽  
Active Transcription

SummaryH2A.Z mono-ubiquitylation has been linked to transcriptional repression, but the mechanisms involved are not well understood. To address this, we developed a biotinylation-based approach to purify ubiquitylated H2A.Z (H2A.Zub) mononucleosomes for biochemical and genome-wide analyses. We observe that H2A.Zub nucleosomes are enriched for the repressive histone post-translational modification H3K27me3, but depleted of H3K4 methylation and other modifications associated with active transcription. ChIP-Seq analyses reveal that H2A.Zub-nucleosomes are enriched over non-expressed genes, and suggest that it is the relative ratio of ubiquitylated to non-ubiquitylated H2A.Z, rather than absolute presence or absence of H2A.Z ubiquitylation, that correlates with gene silencing. Finally, we observe that H2A.Zub-eniched mononucleosomes preferentially co-purify with transcriptional silencing factors as well as proteins involved in higher order chromatin organization such as CTCF and cohesin. Collectively, these results suggest an important role for H2A.Z ubiquitylation in mediating global transcriptional repression through its recruitment of silencing factors and nuclear architectural proteins.

scholarly journals Experimental and Bioinformatic upgrade for genome-wide mapping of nucleosomes in Trypanosoma cruzi

2021 ◽  
Author(s):  
Paula Beati ◽  
Milena Massimino Stepnicka ◽  
Salome Vilchez Larrea ◽  
Guillermo Daniel Alonso ◽  
Josefina Ocampo
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Cycle Progression ◽  
Repetitive Sequences ◽  
Nucleosome Position ◽  
Regulatory Elements ◽  
Histone Variants ◽  
Chromatin Organization ◽  
Micrococcal Nuclease ◽  
Cell Manipulation ◽  
Genome Wide

In Trypanosoma cruzi, as in every eukaryotic cell, DNA is packaged into chromatin by octamers of histone proteins that constitute nucleosomes. Besides compacting DNA, nucleosomes control DNA dependent processes by modulating the access of DNA binding proteins to regulatory elements on the DNA; or by providing the platform for additional layers of regulation given by histone variants and histone post-translational modifications. In trypanosomes, protein coding genes are constitutively transcribed as polycistronic units. Therefore, gene expression is controlled mainly post transcriptionally. However, chromatin organization and the histone code influence transcription, cell cycle progression, replication and DNA repair. Hence, determining nucleosome position is of uppermost importance to understand the peculiarities of these processes in trypanosomes. Digestion of chromatin with micrococcal nuclease followed by deep sequencing has been widely applied for genome-wide mapping of nucleosomes in several organisms. Nonetheless, this parasite presents numerous singularities. On one hand, special growth conditions and cell manipulation are required. On the other hand, chromatin organization shows some uniqueness that demands a specially designed analytical approach. An additional entanglement is given by the nature of its genome harboring a large content of repetitive sequences and the poor quality of the genome assembly and annotation of many strains. Here, we adapted this broadly used method to the hybrid reference strain, CL Brener. Particularly, we developed an exhaustive and thorough computational workflow for data analysis, highlighting the relevance of using its whole genome as a reference instead of the commonly used Esmeraldo-like haplotype. Moreover, the performance of two aligners, Bowtie2 and HISAT2 was tested to find the most appropriate tool to map any genomic read to reference genomes bearing this complexity.

scholarly journals Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization

Cell Research ◽  
2012 ◽  
Vol 22 (3) ◽  
pp. 490-503 ◽  
Author(s):  
Iouri Chepelev ◽  
Gang Wei ◽  
Dara Wangsa ◽  
Qingsong Tang ◽  
Keji Zhao
Keyword(s):  
Higher Order ◽  
Chromatin Organization ◽  
Genome Wide
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