scholarly journals Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells

2018 ◽  
Vol 218 (2) ◽  
pp. 433-444 ◽  
Author(s):  
Brandon H. Toyama ◽  
Rafael Arrojo e Drigo ◽  
Varda Lev-Ram ◽  
Ranjan Ramachandra ◽  
Thomas J. Deerinck ◽  
...  
Keyword(s):  
Regulatory Proteins ◽  
Dependent Manner ◽  
Host Organism ◽  
Nuclear Pores ◽  
Silent Gene ◽  
Quiescent Cells ◽  
Formidable Challenge ◽  
Genome Wide ◽  
Postmitotic Cells ◽  
Turn Over

Many adult tissues contain postmitotic cells as old as the host organism. The only organelle that does not turn over in these cells is the nucleus, and its maintenance represents a formidable challenge, as it harbors regulatory proteins that persist throughout adulthood. Here we developed strategies to visualize two classes of such long-lived proteins, histones and nucleoporins, to understand the function of protein longevity in nuclear maintenance. Genome-wide mapping of histones revealed specific enrichment of long-lived variants at silent gene loci. Interestingly, nuclear pores are maintained by piecemeal replacement of subunits, resulting in mosaic complexes composed of polypeptides with vastly different ages. In contrast, nondividing quiescent cells remove old nuclear pores in an ESCRT-dependent manner. Our findings reveal distinct molecular strategies of nuclear maintenance, linking lifelong protein persistence to gene regulation and nuclear integrity.

scholarly journals Genome-Wide Identification and Expression Profiling of the PDI Gene Family Reveals Their Probable Involvement in Abiotic Stress Tolerance in Tomato (Solanum lycopersicum L.)

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 23
Author(s):  
Antt Htet Wai ◽  
Muhammad Waseem ◽  
A B M Mahbub Morshed Khan ◽  
Ujjal Kumar Nath ◽  
Do Jin Lee ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Gene Family ◽  
Stress Tolerance ◽  
Solanum Lycopersicum ◽  
Expression Profiling ◽  
Abiotic Stress Tolerance ◽  
Dependent Manner ◽  
Solanum Lycopersicum L ◽  
Genome Wide ◽  
Protein Disulfide

Protein disulfide isomerases (PDI) and PDI-like proteins catalyze the formation and isomerization of protein disulfide bonds in the endoplasmic reticulum and prevent the buildup of misfolded proteins under abiotic stress conditions. In the present study, we conducted the first comprehensive genome-wide exploration of the PDI gene family in tomato (Solanum lycopersicum L.). We identified 19 tomato PDI genes that were unevenly distributed on 8 of the 12 tomato chromosomes, with segmental duplications detected for 3 paralogous gene pairs. Expression profiling of the PDI genes revealed that most of them were differentially expressed across different organs and developmental stages of the fruit. Furthermore, most of the PDI genes were highly induced by heat, salt, and abscisic acid (ABA) treatments, while relatively few of the genes were induced by cold and nutrient and water deficit (NWD) stresses. The predominant expression of SlPDI1-1, SlPDI1-3, SlPDI1-4, SlPDI2-1, SlPDI4-1, and SlPDI5-1 in response to abiotic stress and ABA treatment suggested they play regulatory roles in abiotic stress tolerance in tomato in an ABA-dependent manner. Our results provide new insight into the structure and function of PDI genes and will be helpful for the selection of candidate genes involved in fruit development and abiotic stress tolerance in tomato.

scholarly journals Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su Yon Jung ◽  
Jeanette C. Papp ◽  
Eric M. Sobel ◽  
Matteo Pellegrini ◽  
Herbert Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Visceral Obesity ◽  
Cumulative Exposure ◽  
Environment Interaction ◽  
Dependent Manner ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Reduction Methods

AbstractMolecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the genome-wide level. With single-nucleotide polymorphisms (SNPs) in the biomarkers and lifestyles together, we further constructed risk profiles to improve predictability for breast cancer. Our earlier genome-wide association gene-environment interaction study used large cohort data from the Women’s Health Initiative Database for Genotypes and Phenotypes Study and identified 88 SNPs associated with CRP and IL-6. For this study, we added an additional 68 SNPs from previous GWA studies, and together with 48 selected lifestyles, evaluated for the association with breast cancer risk via a 2-stage multimodal random survival forest and generalized multifactor dimensionality reduction methods. Overall and in obesity strata (by body mass index, waist, waist-to-hip ratio, exercise, and dietary fat intake), we identified the most predictive genetic and lifestyle variables. Two SNPs (SALL1 rs10521222 and HLA-DQA1 rs9271608) and lifestyles, including alcohol intake, lifetime cumulative exposure to estrogen, and overall and visceral obesity, are the most common and strongest predictive markers for breast cancer across the analyses. The risk profile that combined those variables presented their synergistic effect on the increased breast cancer risk in a gene–lifestyle dose-dependent manner. Our study may contribute to improved predictability for breast cancer and suggest potential interventions for the women with the risk genotypes and lifestyles to reduce their breast cancer risk.

scholarly journals Identification and Characterization of OscR, a Transcriptional Regulator Involved in Osmolarity Adaptation in Vibrio cholerae

2009 ◽  
Vol 191 (13) ◽  
pp. 4082-4096 ◽  
Author(s):  
Nicholas J. Shikuma ◽  
Fitnat H. Yildiz
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Transcriptional Regulator ◽  
Dependent Manner ◽  
Genome Wide ◽  
Low Salt ◽  
Adaptation Response ◽  
Matrix Production ◽  
Identification And Characterization

ABSTRACT Vibrio cholerae is a facultative human pathogen. In its aquatic habitat and as it passes through the digestive tract, V. cholerae must cope with fluctuations in salinity. We analyzed the genome-wide transcriptional profile of V. cholerae grown at different NaCl concentrations and determined that the expression of compatible solute biosynthesis and transporter genes, virulence genes, and genes involved in adhesion and biofilm formation is differentially regulated. We determined that salinity modulates biofilm formation, and this response was mediated through the transcriptional regulators VpsR and VpsT. Additionally, a transcriptional regulator controlling an osmolarity adaptation response was identified. This regulator, OscR (osmolarity controlled regulator), was found to modulate the transcription of genes involved in biofilm matrix production and motility in a salinity-dependent manner. oscR mutants were less motile and exhibited enhanced biofilm formation only under low-salt conditions.

Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessilyn Dunn ◽  
Haiwei Qiu ◽  
Soyeon Kim ◽  
Daudi Jjingo ◽  
Ryan Hoffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Western Diet ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

scholarly journals Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sarah G Swygert ◽  
Dejun Lin ◽  
Stephanie Portillo-Ledesma ◽  
Po-Yen Lin ◽  
Dakota R Hunt ◽  
...  
Keyword(s):  
Chromatin Fiber ◽  
State Transitions ◽  
Chromatin Domain ◽  
Global Changes ◽  
Histone H4 ◽  
Mitotic Chromosomes ◽  
Quiescent Cells ◽  
Genome Wide ◽  
Dividing Cells ◽  
The Relationship

A longstanding hypothesis is that chromatin fiber folding mediated by interactions between nearby nucleosomes represses transcription. However, it has been difficult to determine the relationship between local chromatin fiber compaction and transcription in cells. Further, global changes in fiber diameters have not been observed, even between interphase and mitotic chromosomes. We show that an increase in the range of local inter-nucleosomal contacts in quiescent yeast drives the compaction of chromatin fibers genome-wide. Unlike actively dividing cells, inter-nucleosomal interactions in quiescent cells require a basic patch in the histone H4 tail. This quiescence-specific fiber folding globally represses transcription and inhibits chromatin loop extrusion by condensin. These results reveal that global changes in chromatin fiber compaction can occur during cell state transitions, and establish physiological roles for local chromatin fiber folding in regulating transcription and chromatin domain formation.

scholarly journals Comprehensive genome-wide analysis of calmodulin-binding transcription activator (CAMTA) in Durio zibethinus and identification of fruit ripening-associated DzCAMTAs

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zahra Iqbal ◽  
Mohammed Shariq Iqbal ◽  
Lalida Sangpong ◽  
Gholamreza Khaksar ◽  
Supaart Sirikantaramas ◽  
...  
Keyword(s):  
Fruit Ripening ◽  
Developmental Process ◽  
Dependent Manner ◽  
Transcription Activator ◽  
Ripening Process ◽  
Post Harvest ◽  
Calmodulin Binding ◽  
Durio Zibethinus ◽  
Genome Wide ◽  
Recognition Motifs

Abstract Background Fruit ripening is an intricate developmental process driven by a highly coordinated action of complex hormonal networks. Ethylene is considered as the main phytohormone that regulates the ripening of climacteric fruits. Concomitantly, several ethylene-responsive transcription factors (TFs) are pivotal components of the regulatory network underlying fruit ripening. Calmodulin-binding transcription activator (CAMTA) is one such ethylene-induced TF implicated in various stress and plant developmental processes. Results Our comprehensive analysis of the CAMTA gene family in Durio zibethinus (durian, Dz) identified 10 CAMTAs with conserved domains. Phylogenetic analysis of DzCAMTAs, positioned DzCAMTA3 with its tomato ortholog that has already been validated for its role in the fruit ripening process through ethylene-mediated signaling. Furthermore, the transcriptome-wide analysis revealed DzCAMTA3 and DzCAMTA8 as the highest expressing durian CAMTA genes. These two DzCAMTAs possessed a distinct ripening-associated expression pattern during post-harvest ripening in Monthong, a durian cultivar native to Thailand. The expression profiling of DzCAMTA3 and DzCAMTA8 under natural ripening conditions and ethylene-induced/delayed ripening conditions substantiated their roles as ethylene-induced transcriptional activators of ripening. Similarly, auxin-suppressed expression of DzCAMTA3 and DzCAMTA8 confirmed their responsiveness to exogenous auxin treatment in a time-dependent manner. Accordingly, we propose that DzCAMTA3 and DzCAMTA8 synergistically crosstalk with ethylene during durian fruit ripening. In contrast, DzCAMTA3 and DzCAMTA8 antagonistically with auxin could affect the post-harvest ripening process in durian. Furthermore, DzCAMTA3 and DzCAMTA8 interacting genes contain significant CAMTA recognition motifs and regulated several pivotal fruit-ripening-associated pathways. Conclusion Taken together, the present study contributes to an in-depth understanding of the structure and probable function of CAMTA genes in the post-harvest ripening of durian.

scholarly journals New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the YRR1 Transcription Factor Regulation System

2002 ◽  
Vol 22 (8) ◽  
pp. 2642-2649 ◽  
Author(s):  
Stéphane Le Crom ◽  
Frédéric Devaux ◽  
Philippe Marc ◽  
Xiaoting Zhang ◽  
W. Scott Moye-Rowley ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcription Factor ◽  
Binding Site ◽  
Time Course ◽  
Target Genes ◽  
Regulation System ◽  
Dependent Manner ◽  
Pleiotropic Drug Resistance ◽  
Genome Wide

ABSTRACT Yrr1p is a recently described Zn2Cys6 transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.

Sequential degradation of proteins from the nuclear envelope during apoptosis

2001 ◽  
Vol 114 (20) ◽  
pp. 3643-3653 ◽  
Author(s):  
Madeleine Kihlmark ◽  
Gabriela Imreh ◽  
Einar Hallberg
Keyword(s):  
Nuclear Envelope ◽  
Apoptotic Cell ◽  
Nuclear Periphery ◽  
Condensed Chromatin ◽  
Nuclear Pore ◽  
Dependent Manner ◽  
Nuclear Pores ◽  
Double Labeling ◽  
Lamin B ◽  
Nuclear Apoptosis

We have produced new antibodies specific for the integral pore membrane protein POM121. Using these antibodies we show that during apoptosis POM121 becomes proteolytically degraded in a caspase-dependent manner. The POM121 antibodies and antibodies specific for other proteins of the nuclear envelope were used in a comparative study of nuclear apoptosis in staurosporine-treated buffalo rat liver cells. Nuclei from these cells were classified in three different stages of apoptotic progression: stage I, moderately condensed chromatin surrounded by a smooth nuclear periphery; stage II, compact patches of condensed chromatin collapsing against a smooth nuclear periphery; stage III, round compact chromatin bodies surrounded by grape-shaped nuclear periphery. We have performed double labeling immunofluorescence microscopy of individual apoptotic cells and quantitative immunoblotting analysis of total proteins from apoptotic cell cultures. The results showed that degradation of nuclear envelope marker proteins occurred in a specific order. POM121 degradation occurred surprisingly early and was initiated before nucleosomal DNA degradation could be detected using TUNEL assay and completed before clustering of the nuclear pores. POM121 was eliminated significantly more rapid compared with NUP153 (a peripheral protein located in the nucleoplasmic basket of the nuclear pore complex) and lamin B (a component of the nuclear lamina). Disappearance of NUP153 and lamin B was coincident with onset of DNA fragmentation and clustering of nuclear pores. By contrast, the peripheral NPC protein p62 was degraded much later. The results suggest that degradation of POM121 may be an important early step in propagation of nuclear apoptosis.

scholarly journals Genome-wide study on the polysomic genetic factors conferring plasticity of flower sexuality in hexaploid persimmon

DNA Research ◽  
2020 ◽  
Vol 27 (3) ◽  
Author(s):  
Kanae Masuda ◽  
Eiji Yamamoto ◽  
Kenta Shirasawa ◽  
Noriyuki Onoue ◽  
Atsushi Kono ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Diospyros Kaki ◽  
Dependent Manner ◽  
Male And Female ◽  
Association Analyses ◽  
Genome Wide ◽  
Allele Dosage ◽  
Partial Inactivation ◽  
In Cis ◽  
Segregating Population

Abstract Sexuality is one of the fundamental mechanisms that work towards maintaining genetic diversity within a species. In diploid persimmons (Diospyros spp.), separated sexuality, the presence of separate male and female individuals (dioecy), is controlled by the Y chromosome-encoded small-RNA gene, OGI. On the other hand, sexuality in hexaploid Oriental persimmon (Diospyros kaki) is more plastic, with OGI-bearing genetically male individuals, able to produce both male and female flowers (monoecy). This is thought to be linked to the partial inactivation of OGI by a retrotransposon insertion, resulting in DNA methylation of the OGI promoter region. To identify the genetic factors regulating branch sexual conversion, genome-wide correlation/association analyses were conducted using ddRAD-Seq data from an F1 segregating population, and using both quantitative and diploidized genotypes, respectively. We found that allelic ratio at the Y-chromosomal region, including OGI, was correlated with male conversion based on quantitative genotypes, suggesting that OGI can be activated in cis in a dosage-dependent manner. Genome-wide association analysis based on diploidized genotypes, normalized for the effect of OGI allele dosage, detected three fundamental loci associated with male conversion. These loci underlie candidate genes, which could potentially act epigenetically for the activation of OGI expression.

scholarly journals TET3 regulates DNA hydroxymethylation of neuroprotective genes following focal ischemia

2020 ◽  
pp. 0271678X2091296
Author(s):  
Kahlilia C Morris-Blanco ◽  
Anil K Chokkalla ◽  
Mario J Bertogliat ◽  
Raghu Vemuganti
Keyword(s):  
Epigenetic Modification ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Dna Hydroxymethylation ◽  
Adult Mice ◽  
Genome Wide ◽  
Endogenous Protection ◽  
Genomic Regions

The 5-hydroxymethylcytosine (5hmC) epigenetic modification is highly enriched in the CNS and a critical modulator of neuronal function and development. We found that cortical 5hmC was enhanced from 5 min to three days of reperfusion following focal ischemia in adult mice. Blockade of the 5hmC-producing enzyme ten-eleven translocase 3 (TET3) increased edema, infarct volume, and motor function impairments. To determine the mechanism by which TET3 provides ischemic neuroprotection, we assessed the genomic regions where TET3 modulates 5hmC. Genome-wide sequencing analysis of differentially hydroxymethylated regions (DhMRs) revealed that focal ischemia robustly increased 5hmC at the promoters of thousands of genes in a TET3-dependent manner. TET3 inhibition reduced 5hmC at the promoters of neuroprotective genes involved in cell survival, angiogenesis, neurogenesis, antioxidant defense, DNA repair, and metabolism demonstrating a role for TET3 in endogenous protection against stroke. The mRNA expression of several genes with known involvement in ischemic neuroprotection were also reduced with TET3 knockdown in both male and female mice, establishing a correlation between decreased promoter 5hmC levels and decreased gene expression. Collectively, our results indicate that TET3 globally increases 5hmC at regulatory regions and overwhelmingly modulates 5hmC in several neuroprotective pathways that may improve outcome after ischemic injury.

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