scholarly journals Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation

2020 ◽  
Vol 48 (21) ◽  
pp. 12151-12168
Author(s):  
Hong-Yeoul Ryu ◽  
Dejian Zhao ◽  
Jianhui Li ◽  
Dan Su ◽  
Mark Hochstrasser
Keyword(s):  
Histone Deacetylase ◽  
Transcription Initiation ◽  
Noncoding Rna ◽  
Histone H2b ◽  
Protein Coding ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Spurious Transcription ◽  
Altered Gene ◽  
Active Genes

Abstract Histones are substrates of the SUMO (small ubiquitin-like modifier) conjugation pathway. Several reports suggest histone sumoylation affects transcription negatively, but paradoxically, our genome-wide analysis shows the modification concentrated at many active genes. We find that trans-tail regulation of histone-H2B ubiquitylation and H3K4 di-methylation potentiates subsequent histone sumoylation. Consistent with the known control of the Set3 histone deacetylase complex (HDAC) by H3K4 di-methylation, histone sumoylation directly recruits the Set3 complex to both protein-coding and noncoding RNA (ncRNA) genes via a SUMO-interacting motif in the HDAC Cpr1 subunit. The altered gene expression profile caused by reducing histone sumoylation matches well to the profile in cells lacking Set3. Histone H2B sumoylation and the Set3 HDAC coordinately suppress cryptic ncRNA transcription initiation internal to mRNA genes. Our results reveal an elaborate co-transcriptional histone crosstalk pathway involving the consecutive ubiquitylation, methylation, sumoylation and deacetylation of histones, which maintains transcriptional fidelity by suppressing spurious transcription.

scholarly journals Gene Expression in Trypanosomatid Parasites

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Santiago Martínez-Calvillo ◽  
Juan C. Vizuet-de-Rueda ◽  
Luis E. Florencio-Martínez ◽  
Rebeca G. Manning-Cela ◽  
Elisa E. Figueroa-Angulo
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Histone Variants ◽  
Protein Coding ◽  
Functional Studies ◽  
Polycistronic Transcription ◽  
General Transcription Factors ◽  
Genome Wide ◽  
Trypanosomatid Parasites

The parasitesLeishmaniaspp.,Trypanosoma brucei,andTrypanosoma cruziare the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids.In silicoanalyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa.

Abstract P323: HIV- and Subclinical Cardiovascular Disease-specific Transcriptomes in Nonclassical Monocytes: The Women’s Interagency HIV Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Juan Lin ◽  
David B Hanna ◽  
Qibin Qi ◽  
tao wang ◽  
Karin A Mueller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Homeostasis ◽  
Checkpoint Inhibition ◽  
Protein Coding ◽  
Altered Gene Expression ◽  
Subclinical Cardiovascular Disease ◽  
Altered Gene ◽  
Transcriptomic Changes ◽  
Insight Into ◽  
Chronic Hiv Infection

Objectives: Nonclassical monocytes (NCM) have patrolling functions relevant to atherosclerosis. While NCM have low surface CXCR4 expression in people with concurrent HIV and CVD (Mueller Cardiovasc Res 2019), the extent of CVD-related gene expression and the pathways involved are unknown. We described the gene transcription signature of NCM to provide insight into potential mechanisms of HIV-associated CVD. Methods: We identified transcriptomic changes in circulating NCM among women with and without chronic HIV infection. CVD was defined by plaques found on B-mode carotid artery ultrasound. The study included 23 HIV - CVD - , 21 HIV + CVD - , 20 HIV - CVD + , and 21 HIV + CVD + women, with these four groups matched by age (median = 45), race (95% minority) and smoking (86% ever-smokers). Using cryopreserved cells, we flow-sorted NCM (CD14 dim CD16+) and deep-sequenced their mRNA (average depth >40 million reads) to identify differentially expressed genes (DEG) contrasting HIV alone, CVD alone, and concurrent HIV + CVD + groups, versus HIV - CVD - , based on FDR-adjusted P<0.05. Results: After filtering to genes with raw counts >10 in >60% of participants, 11,343 protein coding genes were analyzed. HIV alone was associated with 10 DEGs on NCM (Figure). Women affected by both HIV and CVD had 93 DEGs, only six of which were shared by the HIV alone DEG signal. CVD alone was associated only with upregulated CDK18, which was also identified as a DEG in the HIV + CVD + group. Conclusion: Concurrent HIV and CVD (HIV + CVD + ) is associated with altered gene expression in NCMs relative to HIV - CVD - , generating responses that involve interleukins (IL32, IL4R), immune checkpoint inhibition (LAG3), chemokines (CCL4, CCL5) and lipid homeostasis (ABCD2).

Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines

2013 ◽  
Vol 36 (5) ◽  
pp. 351-362 ◽  
Author(s):  
Floor A.M. Duijkers ◽  
Renee X. de Menezes ◽  
Inès J. Goossens-Beumer ◽  
Dominique J.P.M. Stumpel ◽  
Pieter Admiraal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Drug Combination ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Epigenetic Drug ◽  
Altered Gene

Human accelerated region 1 noncoding RNA is repressed by REST in Huntington's disease

2010 ◽  
Vol 41 (3) ◽  
pp. 269-274 ◽  
Author(s):  
Rory Johnson ◽  
Nadine Richter ◽  
Ralf Jauch ◽  
Philip M. Gaughwin ◽  
Chiara Zuccato ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Transcriptional Repression ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Target Genes ◽  
Protein Coding ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Dna Regulatory Motifs

In the neurons of Huntington's disease (HD) patients, gene regulatory networks are disrupted by aberrant nuclear localization of the master transcriptional repressor REST. Emerging evidence suggests that, in addition to protein-coding genes, noncoding RNAs (ncRNAs) may also contribute to neurodegenerative processes. To discover ncRNAs that are involved in HD, we screened genome-wide data for novel, noncoding targets of REST. This identified human accelerated region 1 (HAR1), a rapidly evolving cis-antisense locus that is specifically transcribed in the nervous system. We show that REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. Consistent with other REST target genes, HAR1 levels are significantly lower in the striatum of HD patients compared with unaffected individuals. These data represent further evidence that noncoding gene expression changes accompany neurodegeneration in Huntington's disease.

scholarly journals A large multiethnic GWAS meta-analysis of cataract identifies new risk loci and sex-specific effects

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hélène Choquet ◽  
Ronald B. Melles ◽  
Deepti Anand ◽  
Jie Yin ◽  
Gabriel Cuellar-Partida ◽  
...  
Keyword(s):  
Meta Analysis ◽  
The Elderly ◽  
The United States ◽  
Altered Gene Expression ◽  
Specific Effects ◽  
Genome Wide ◽  
Altered Gene ◽  
Mouse Lens ◽  
Insight Into ◽  
Gene Perturbation

AbstractCataract is the leading cause of blindness among the elderly worldwide and cataract surgery is one of the most common operations performed in the United States. As the genetic etiology of cataract formation remains unclear, we conducted a multiethnic genome-wide association meta-analysis, combining results from the GERA and UK Biobank cohorts, and tested for replication in the 23andMe research cohort. We report 54 genome-wide significant loci, 37 of which were novel. Sex-stratified analyses identified CASP7 as an additional novel locus specific to women. We show that genes within or near 80% of the cataract-associated loci are significantly expressed and/or enriched-expressed in the mouse lens across various spatiotemporal stages as per iSyTE analysis. Furthermore, iSyTE shows 32 candidate genes in the associated loci have altered gene expression in 9 different gene perturbation mouse models of lens defects/cataract, suggesting their relevance to lens biology. Our work provides further insight into the complex genetic architecture of cataract susceptibility.

scholarly journals Silent crickets reveal the genomic footprint of recent adaptive trait loss

2018 ◽  
Author(s):  
Sonia Pascoal ◽  
Judith E. Risse ◽  
Xiao Zhang ◽  
Mark Blaxter ◽  
Timothee Cezard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Loss ◽  
Sexual Signal ◽  
Adaptive Trait ◽  
Field Crickets ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene ◽  
High Density Linkage Map ◽  
Mutational Effect

Secondary trait loss is widespread and has profound consequences, from generating diversity to driving adaptation. Sexual trait loss is particularly common. Its genomic impact is challenging to reconstruct because most reversals occurred in the distant evolutionary past and must be inferred indirectly, and questions remain about the extent of disruption caused by pleiotropy, altered gene expression and loss of homeostasis. We tested the genomic signature of recent sexual signal loss in Hawaiian field crickets, Teleogryllus oceanicus. Song loss is controlled by a sex-linked Mendelian locus, flatwing, which feminises male wings by erasing sound-producing veins. This variant spread rapidly under pressure from an eavesdropping parasitoid fly. We sequenced, assembled and annotated the T. oceanicus genome, produced a high-density linkage map, and localised flatwing on the X chromosome. We characterised pleiotropic effects of flatwing, including changes in embryonic gene expression and alteration of another sexual signal, chemical pheromones. Song loss is associated with pleiotropy, hitchhiking and genome-wide regulatory disruption which feminises flatwing male pheromones. The footprint of recent adaptive trait loss illustrates R. A. Fisher's influential prediction that variants with large mutational effect sizes can invade genomes during the earliest stages of adaptation to extreme pressures, despite having severely disruptive genomic consequences.

199 IN VITRO-DEVELOPED BOVINE BLASTOCYSTS ARE MARKED WITH ABERRANT HYPER- AND HYPO-METHYLATED GENOMIC REGIONS

2015 ◽  
Vol 27 (1) ◽  
pp. 190
Author(s):  
D. Salilew-Wondim ◽  
M. Hoelker ◽  
U. Besenfelder ◽  
V. Havlicek ◽  
F. Rings ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Patterns ◽  
Proximal Promoter ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene ◽  
Genomic Regions

Most often, in vitro produced embryos display poor quality and altered gene expression patterns compared to their in vivo counterparts. Aberrant DNA methylation occurring during in vitro embryo development is believed to be one of the multifaceted factors which may cause altered gene expression and poor embryo quality. Here, we investigated the genome-wide DNA methylation patterns of in vitro derived embryos using the recently developed Bovine EmbryoGENE Methylation Platform (BEGMP) array (Shojaei Saadi et al. BMC Genomics 2014 15, 451. doi: 10.1186/1471-2164-15-451) to unravel the aberrantly methylated genomic region in in vitro developed embryos. For this, in vitro and in vivo produced blastocysts were produced and used for genome-wide DNA methylation analysis. In vitro blastocysts were produced from oocytes retrieved from ovaries collected from the local abattoir and matured, fertilized, and cultured in vitro using SOF media. The in vivo blastocysts were produced by superovulation and AI of Simmental heifers followed by uterine flushing. Genomic DNA (gDNA) was then isolated from four replicates (each 10 blastocysts) of in vivo and in vitro derived blastocysts using Allprep DNA/RNA micro kit (Qiagen, Valencia, CA, USA) and the gDNA was then fragmented using the MseI enzyme. Following this, MseLig21 and MseLig were ligated to the MseI-digested genomic fragments in the presence of Ligase enzyme. Methyl-sensitive enzymes, HpaII, AciI, and Hinp1I, were used to cleave unmethlayted genomic regions within the MseI-MseI region of the fragmented DNA. The gDNA was subjected to two rounds of ligation-mediated polymerase chain reaction (LM-PCR) amplification. After removal of the adapters, the amplified gDNA samples from in vivo or in vitro groups were labelled either Cy-3 or Cy-5 dyes in dye-swap design using ULS Fluorescent gDNA labelling kit (Kreatech Biotechnology BV, Amsterdam, The Netherlands). Hybridization was performed for 40 h at 65°C. Slides were scanned using Agilent's High-Resolution C Scanner (Agilent Technologies Inc., Santa Clara, CA, USA) and features were extracted with Agilent's Feature Extraction software (Agilent Technologies Inc.). The results have shown that from a total of 414 566 probes harboured by the BEGMP array, 248 453 and 253 147 probes were detected in in vitro and in vivo derived blastocysts, respectively. Data analysis using the linear modelling for microarray (LIMMA) package and R software (The R Project for Statistical Computing, Vienna, Austria) revealed a total of 3434 differentially methylated regions (DMRs; Fold change ≥1.5, P-value <0.05), of which 42 and 58% were hyper- and hypo-methylated, respectively, in in vitro derived blastocysts compared to their in vivo counterparts. The DMRs were found to be localised in the intronic, exonic, promoter, proximal promoter, and distal promoter, and some of the probes did not have nearby genes. In addition, 10.8% of the DMRs were found to be stretched in short, long, or intermediate CpG islands. Thus, this study demonstrated genome-wide dysregulation in the epigenome landscape of in vitro-derived embryos by the time they reach to the blastocysts stage.

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