Faculty Opinions recommendation of Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction.

Author(s):  
Andrea Mattevi
2011 ◽  
Vol 7 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Beat Fierz ◽  
Champak Chatterjee ◽  
Robert K McGinty ◽  
Maya Bar-Dagan ◽  
Daniel P Raleigh ◽  
...  

2018 ◽  
Author(s):  
Brandon D. Fields ◽  
Scott Kennedy

AbstractDNA is organized and compacted into higher-order structures in order to fit within nuclei and to facilitate proper gene regulation. Mechanisms by which higher order chromatin structures are established and maintained are poorly understood. In C. elegans, nuclear-localized small RNAs engage the nuclear RNAi machinery to regulate gene expression and direct the post-translational modification of histone proteins. Here we confirm a recent report suggesting that nuclear small RNAs are required to initiate or maintain chromatin compaction states in C. elegans germ cells. Additionally, we show that experimentally provided small RNAs are sufficient to direct chromatin compaction and that this compaction requires the small RNA-binding Argonaute NRDE-3, the pre-mRNA associated factor NRDE-2, and the HP1-like protein HPL-2. Our results show that small RNAs, acting via the nuclear RNAi machinery and an HP1-like protein, are capable of driving chromatin compaction in C. elegans.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Aniket Patankar ◽  
Rahul Gajbhiye ◽  
Suchitra Surve ◽  
Priyanka Parte

Abstract Background Biological relevance of the major testis specific histone H2B variant (TH2B) in sperm is not fully understood. Studies in TH2A/TH2B double knockout male mice indicate its role in chromatin compaction and male fertility. Additionally, the presence of TH2B and TH2A reportedly generates more dynamic nucleosomes, leading to an open chromatin structure characteristic of transcriptionally active genome. Given that mature human sperm are transcriptionally and translationally inactive, the presence of TH2B in mature sperm is intriguing. To address its role in sperm, we investigated the genome-wide localization of TH2B in sperm of fertile men. Results We have identified the genomic loci associated with TH2B in fertile human sperm by ChIP-seq analysis. Bioinformatic analysis revealed ~ 5% sperm genome and 5527 genes to be associated with TH2B. Out of these 105 (1.9%) and 144 (2.6%) genes showed direct involvement in sperm function and early embryogenesis, respectively. Chromosome wide analysis for TH2B distribution indicated its least distribution on X and Y chromosomes and varied distribution on autosomes. TH2B showed relatively higher percentage of gene association on chromosome 4, 18, 3 and 2. TH2B enrichment was more in promoter and gene body region. Gene Ontology (GO) analysis revealed signal transduction and associated kinase activity as the most enriched biological and molecular function, respectively. We also observed the enrichment of TH2B at developmentally important loci, such as HOXA and HOXD and on genes required for normal sperm function, few of which were validated by ChIP-qPCR. The relative expression of these genes was altered in particular subgroup of infertile men showing abnormal chromatin packaging. Chromatin compaction positively correlated with sperm- motility, concentration, viability and with transcript levels of PRKAG2 and CATSPER B. Conclusion ChIP-seq analysis of TH2B revealed a putative role of TH2B in sperm function and embryo development. Altered expression of TH2B associated genes in infertile individuals with sperm chromatin compaction defects indicates involvement of TH2B in transcriptional regulation of these genes in post meiotic male germ cells. This altered transcriptome may be a consequence or cause of abnormal nuclear remodeling during spermiogenesis.


2017 ◽  
Author(s):  
Matthew Robert Paul ◽  
Tovah Elise Markowitz ◽  
Andreas Hochwagen ◽  
Sevinç Ercan

AbstractCondensins are broadly conserved chromosome organizers that function in chromatin compaction and transcriptional regulation, but to what extent these two functions are linked has remained unclear. Here, we analyzed the effect of condensin inactivation on genome compaction and global gene expression in the yeast Saccharomyces cerevisiae. Spike-in-controlled 3C-seq analysis revealed that acute condensin inactivation leads to a global decrease in close-range chromosomal interactions as well as more specific losses of homotypic tRNA gene clustering. In addition, a condensin-rich topologically associated domain between the ribosomal DNA and the centromere on chromosome XII is lost upon condensin inactivation. Unexpectedly, these large-scale changes in chromosome architecture are not associated with global changes in transcript levels as determined by spike-in-controlled mRNA-seq analysis. Our data suggest that the global transcriptional program of S. cerevisiae is resistant to condensin inactivation and the associated profound changes in genome organization.Significance StatementGene expression occurs in the context of higher-order chromatin organization, which helps compact the genome within the spatial constraints of the nucleus. To what extent higher-order chromatin compaction affects gene expression remains unknown. Here, we show that gene expression and genome compaction can be uncoupled in the single-celled model eukaryote Saccharomyces cerevisiae. Inactivation of the conserved condensin complex, which also organizes the human genome, leads to broad genome decompaction in this organism. Unexpectedly, this reorganization has no immediate effect on the transcriptome. These findings indicate that the global gene expression program is robust to large-scale changes in genome architecture in yeast, shedding important new light on the evolution and function of genome organization in gene regulation.


PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e22209 ◽  
Author(s):  
Chen-Yi Wang ◽  
Chia-Yin Hua ◽  
Hsiang-En Hsu ◽  
Chia-Ling Hsu ◽  
Hsin-Yi Tseng ◽  
...  

2020 ◽  
Author(s):  
Marion Herbette ◽  
Valérie Robert ◽  
Aymeric Bailly ◽  
Loïc Gely ◽  
Robert Feil ◽  
...  

Abstract Background Histone-modifying activities play important roles in gene expression and influence higher-order genome organization. SET1/COMPASS (Complex Proteins Associated with Set1) deposits h istone H3 lysine 4 (H3K4) methylation at promoter regions and is associated with context-dependent effects on gene expression. Whether it also contributes to higher-order chromosome organization has not been explored. Results Using a quantitative FRET (Förster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) approach to assay nanometer scale chromatin compaction in live animals, we reveal a novel role for SET1/COMPASS in structuring meiotic chromosomes in the C. elegans germline . Inactivation of SET-2, the C. elegans homologue of SET1, strongly enhanced chromosome organization defects and loss of fertility resulting from depletion of condensin-II, and aggravated defects in chromosome morphology resulting from inactivation of topoisomerase II, another major structural component of chromosomes. Loss of CFP-1, the chromatin targeting subunit of COMPASS, similarly affected germline chromatin compaction measured by FLIM-FRET and enhanced condensin-II knock-down phenotypes. Conclusions The data presented here are consistent with a role of SET1/ COMPASS in shaping meiotic chromosomes in the C. elegans germline. This new insight has important implications for how c hromatin-modifying complexes and histone modifications may cooperate with non histone-proteins to achieve proper chromosome organization, not only in meiosis, but also in mitosis.


2020 ◽  
Author(s):  
Harry Fischl ◽  
David McManus ◽  
Roel Oldenkamp ◽  
Lothar Schermelleh ◽  
Jane Mellor ◽  
...  

AbstractCooling patients to sub-physiological temperatures is an integral part of modern medicine. We show that cold exposure induces temperature-specific changes to the higher-order chromatin and gene expression profiles of human cells. These changes are particularly dramatic at 18°C, a temperature synonymous with that experienced by patients undergoing controlled deep-hypothermia during surgery. Cells exposed to 18°C exhibit largely nuclear-restricted transcriptome changes. These include the nuclear accumulation of core circadian clock suppressor gene transcripts, most notably REV-ERBα. This response is accompanied by compaction of higher-order chromatin and hindrance of mRNPs from engaging nuclear pores. Rewarming reverses chromatin compaction and releases the transcripts into the cytoplasm, triggering a pulse of suppressor gene proteins that resets the circadian clock. We show that cold-induced upregulation of REV-ERBα alone is sufficient to trigger this resetting. Our findings uncover principles of the cellular cold-response that must be considered for current and future applications involving therapeutic deep-hypothermia.


2019 ◽  
Vol 42 ◽  
Author(s):  
Daniel J. Povinelli ◽  
Gabrielle C. Glorioso ◽  
Shannon L. Kuznar ◽  
Mateja Pavlic

Abstract Hoerl and McCormack demonstrate that although animals possess a sophisticated temporal updating system, there is no evidence that they also possess a temporal reasoning system. This important case study is directly related to the broader claim that although animals are manifestly capable of first-order (perceptually-based) relational reasoning, they lack the capacity for higher-order, role-based relational reasoning. We argue this distinction applies to all domains of cognition.


Author(s):  
G.F. Bastin ◽  
H.J.M. Heijligers

Among the ultra-light elements B, C, N, and O nitrogen is the most difficult element to deal with in the electron probe microanalyzer. This is mainly caused by the severe absorption that N-Kα radiation suffers in carbon which is abundantly present in the detection system (lead-stearate crystal, carbonaceous counter window). As a result the peak-to-background ratios for N-Kα measured with a conventional lead-stearate crystal can attain values well below unity in many binary nitrides . An additional complication can be caused by the presence of interfering higher-order reflections from the metal partner in the nitride specimen; notorious examples are elements such as Zr and Nb. In nitrides containing these elements is is virtually impossible to carry out an accurate background subtraction which becomes increasingly important with lower and lower peak-to-background ratios. The use of a synthetic multilayer crystal such as W/Si (2d-spacing 59.8 Å) can bring significant improvements in terms of both higher peak count rates as well as a strong suppression of higher-order reflections.


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