scholarly journals Regulation of Gene Transcription by the Histone H2A N-Terminal Domain

2007 ◽  
Vol 27 (21) ◽  
pp. 7641-7648 ◽  
Author(s):  
Michael A. Parra ◽  
John J. Wyrick
Keyword(s):  
Gene Transcription ◽  
Microarray Data ◽  
Transcriptional Repression ◽  
Dna Microarrays ◽  
Reporter Genes ◽  
Histone H2a ◽  
Terminal Domain ◽  
Genome Wide ◽  
Genome Wide Expression

ABSTRACT Histone N-terminal domains play critical roles in regulating chromatin structure and gene transcription. Relatively little is known, however, about the role of the histone H2A N-terminal domain in transcription regulation. We have used DNA microarrays to characterize the changes in genome-wide expression caused by mutations in the N-terminal domain of histone H2A. Our results indicate that the N-terminal domain of histone H2A functions primarily to repress the transcription of a large subset of the Saccharomyces cerevisiae genome and that most of the H2A-repressed genes are also repressed by the histone H2B N-terminal domain. Using the histone H2A microarray data, we selected three reporter genes (BNA1, BNA2, and GCY1), which we subsequently used to map regions in the H2A N-terminal domain responsible for this transcriptional repression. These studies revealed that a small subdomain in the H2A N-terminal tail, comprised of residues 16 to 20, is required for the transcriptional repression of these reporter genes. Deletion of either the entire histone H2A N-terminal domain or just this small subdomain imparts sensitivity to UV irradiation. Finally, we show that two residues in this H2A subdomain, serine-17 and arginine-18, are specifically required for the transcriptional repression of the BNA2 reporter gene.

scholarly journals Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jing Shen ◽  
Shuang Wang ◽  
Abby B. Siegel ◽  
Helen Remotti ◽  
Qiao Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Potential Role ◽  
Dna Hypermethylation ◽  
Two Phase ◽  
Genome Wide ◽  
Phase Study ◽  
A Genome ◽  
Genome Wide Expression ◽  
Inactive Chromatin

Background.Previous studies, including ours, have examined the regulation of microRNAs (miRNAs) by DNA methylation, but whether this regulation occurs at a genome-wide level in hepatocellular carcinoma (HCC) is unclear.Subjects/Methods.Using a two-phase study design, we conducted genome-wide screening for DNA methylation and miRNA expression to explore the potential role of methylation alterations in miRNAs regulation.Results.We found that expressions of 25 miRNAs were statistically significantly different between tumor and nontumor tissues and perfectly differentiated HCC tumor from nontumor. Six miRNAs were overexpressed, and 19 were repressed in tumors. Among 133 miRNAs with inverse correlations between methylation and expression, 8 miRNAs (6%) showed statistically significant differences in expression between tumor and nontumor tissues. Six miRNAs were validated in 56 additional paired HCC tissues, and significant inverse correlations were observed for miR-125b and miR-199a, which is consistent with the inactive chromatin pattern found in HepG2 cells.Conclusion.These data suggest that the expressions of miR-125b and miR-199a are dramatically regulated by DNA hypermethylation that plays a key role in hepatocarcinogenesis.

scholarly journals Comparative proteomics and global genome-wide expression data implicate role of ARMC8 in lung cancer

2015 ◽  
Vol 16 (9) ◽  
pp. 3691-3696 ◽  
Author(s):  
Asif Amin ◽  
Shoiab Bukhari ◽  
Taseem A Mokhdomi ◽  
Naveed Anjum ◽  
Asrar H Wafai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Comparative Proteomics ◽  
Expression Data ◽  
Genome Wide ◽  
Genome Wide Expression

Transcriptomics of placental tissue: identification of molecular mechanisms and measures for targeted therapy of grate obstetric syndromes

2020 ◽  
pp. 73-75
Author(s):  
Е.А. Трифонова ◽  
А.В. Марков ◽  
И.А. Степанов ◽  
Е.В. Ижойкина ◽  
В.А. Степанов
Keyword(s):  
Expression Profiling ◽  
Protein Modification ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Placental Tissue ◽  
Master Regulators ◽  
Tissue Identification ◽  
Genome Wide ◽  
Genome Wide Expression

Многочисленными исследованиями показано, что ключевые патогенетические механизмы больших акушерских синдромов (БАС) связаны с нарушением процессов плацентации. В связи с чем, целью нашей работы являлся поиск новых генетических маркеров этих гестационных осложнений на основе интегративного анализа данных, полученных при полногеномном экспрессионном профилировании плацентарной ткани. Нами выявлено 64 гена, транскрипционная активность которых статистически значимо изменяется как минимум при двух заболеваниях группы БАС. Показана значимая роль нарушения межклеточных взаимодействий и регуляции модификации белков в плацентарной ткани при развитии изученных патологических состояний беременности, идентифицированы мастер-регуляторы, рассматриваемые в качестве потенциальных терапевтических мишеней. It is shown that the key pathogenetic mechanisms of grate obstetric syndromes (GOS) are associated with impaired placentation. The aim of the work was to search for new genetic markers of GOS on the basis of integrative analysis of genome-wide expression profiling data. We found that the transcriptional activity of 64 genes changes in at least two GOS diseases. The significant role of disturbance of intercellular interactions and regulation of protein modification in placental tissue during the development of the pregnancy complications is shown. Master regulators that are potential therapeutic targets have been identified.

scholarly journals Genome-wide Expression Analyses ofCampylobacter jejuniNCTC11168 Reveals Coordinate Regulation of Motility and Virulence byflhA

2004 ◽  
Vol 279 (19) ◽  
pp. 20327-20338 ◽  
Author(s):  
Catherine D. Carrillo ◽  
Eduardo Taboada ◽  
John H. E. Nash ◽  
Patricia Lanthier ◽  
John Kelly ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Dna Microarrays ◽  
Expression Patterns ◽  
Regulatory System ◽  
Toxin Production ◽  
Gene Encoding ◽  
Coordinate Regulation ◽  
Genome Wide ◽  
Transcript Profiles ◽  
Genome Wide Expression

We examined two variants of the genome-sequenced strain,Campylobacter jejuniNCTC11168, which show marked differences in their virulence properties including colonization of poultry, invasion of Caco-2 cells, and motility. Transcript profiles obtained from whole genome DNA microarrays and proteome analyses demonstrated that these differences are reflected in late flagellar structural components and in virulence factors including those involved in flagellar glycosylation and cytolethal distending toxin production. We identified putative σ28and σ54promoters for many of the affected genes and found that greater differences in expression were observed for σ28-controlled genes. Inactivation of the gene encoding σ28,fliA, resulted in an unexpected increase in transcripts with σ54promoters, as well as decreased transcription of σ28-regulated genes. This was unlike the transcription profile observed for the attenuatedC. jejunivariant, suggesting that the reduced virulence of this organism was not entirely due to impaired function of σ28. However, inactivation offlhA, an important component of the flagellar export apparatus, resulted in expression patterns similar to that of the attenuated variant. These findings indicate that the flagellar regulatory system plays an important role in campylobacter pathogenesis and thatflhAis a key element involved in the coordinate regulation of late flagellar genes and of virulence factors inC. jejuni.

Role of OsNPR1 in rice defense program as revealed by genome-wide expression analysis

2010 ◽  
Vol 74 (6) ◽  
pp. 549-562 ◽  
Author(s):  
Shoji Sugano ◽  
Chang-Jie Jiang ◽  
Shin-Ichi Miyazawa ◽  
Chisato Masumoto ◽  
Katsumi Yazawa ◽  
...  
Keyword(s):  
Expression Analysis ◽  
Genome Wide ◽  
Genome Wide Expression

scholarly journals Active enhancers strengthen TAD insulation by bRNA mediated CTCF enrichment at the TAD boundaries

2021 ◽  
Author(s):  
Zubairul Islam ◽  
Bharath Saravanan ◽  
Kaivalya Walavalkar ◽  
Umer Farooq ◽  
Anurag Kumar Singh ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Transcriptional Activity ◽  
Ctcf Binding ◽  
Functional Roles ◽  
Topologically Associating Domains ◽  
Genome Wide ◽  
Direct Association ◽  
Per Se

The genome is partitioned into Topologically Associating Domains (TADs). About half of the boundaries of these TADs exhibit transcriptional activity and are correlated with better TAD insulation. However, the role of these transcripts per se in TAD insulation, enhancer:promoter interactions and transcription remain unknown. Here we investigate the functional roles of these bRNAs (boundary-RNA) in boundary insulation and consequent effects on enhancer-promoter interactions and TAD transcription genome-wide and on disease relevant INK4a/ARF TAD. Using series of CTCF sites deletion and bRNA knockdown approaches at this TAD boundary, we show a direct association of CTCF with bidirectional bRNAs where the loss of bRNA triggers the concomitant loss of: CTCF clustering at TAD boundary, its insulation, enhancer:promoter interactions and gene transcription within the targeted TAD. In search of what regulates bRNA expression itself, we used another series of enhancer deletions and CRISPRi on promoters within INK4a/ARF TAD and observed that indeed, enhancers interact with boundaries and positively regulate the bRNA transcription at TAD boundaries. In return, the bRNAs recruit/stabilise the CTCF even on weaker motifs within these boundaries and supports CTCF binding in clusters, therefore enhancing TAD insulation which favors the intra-TAD enhancer:promoter interactions and robust gene transcription. Functionally, eRNAs within the boundaries are repurposed as more stable bRNAs and their knockdown exactly mimics the boundary loss. Furthermore, transcribing boundaries exhibit high TAD transcription in TCGA tumor datasets. Together, these results show that active enhancers directly mediate better insulation of TADs by activating the transcription at TAD boundaries. These transcripts trigger CTCF clustering at the boundary resulting in better insulation which favours robust intra-TAD enhancer:promoter interactions to activate the gene transcription.

scholarly journals Regulation of Pol II Pausing Is Involved in Daily Gene Transcription in the Mouse Liver

2018 ◽  
Vol 33 (4) ◽  
pp. 350-362 ◽  
Author(s):  
Jialou Zhu ◽  
Chengwei Li ◽  
Changxia Gong ◽  
Xiaodong Li
Keyword(s):  
Gene Transcription ◽  
Mouse Liver ◽  
Phase Distribution ◽  
Gene Body ◽  
Pol Ii ◽  
Genome Wide ◽  
A Genome ◽  
Pol Ii Pausing ◽  
Transcriptional Output

The circadian clock orchestrates gene expression rhythms. Regulation at the level of gene transcription is essential for molecular and cellular rhythms. Pol II pause release is a critical step of transcription regulation. However, whether and how Pol II pause release is regulated during daily transcription have not been characterized. In this study, we performed Pol II ChIP-seq across the day in the mouse liver and quantitatively analyzed binding signals within the transcription start site (TSS) region and the gene body. We frequently found discordant changes between Pol II near the TSS ([Pol II]TSS, paused Pol II) and that within the gene body ([Pol II]GB, transcribing Pol II) across the genome, with only [Pol II]GB always reflecting transcription of clock and clock-controlled genes. Accordingly, Pol II traveling ratios of more than 7000 genes showed significant daily changes (>1.5-fold). Therefore, there is widespread regulation of Pol II pausing in the mouse liver. Interestingly, gene transcription rhythms exhibited a bimodal phase distribution. The transcription of ~400 genes peaked near ZT0, coincident with a genome-wide increase in [Pol II]TSS and traveling ratio (TR). The transcription of ~300 other genes peaked ~12 h later, when there was a global decrease in [Pol II]TSS and TR. ChIP-seq against TATA-binding protein (Tbp), a preinitiation complex (PIC) component, revealed that Pol II recruitment mainly played an indirect role in transcriptional output, with transcriptional termination and pause release functioning prominently in determining the fate of initiated Pol II and its pausing status. Taken together, our results revealed a critical, albeit complex role of Pol II pausing control in regulating the temporal output of gene transcription.

scholarly journals Dynamic Distribution of SeqA Protein across the Chromosome of Escherichia coli K-12

mBio ◽  
2010 ◽  
Vol 1 (1) ◽  
Author(s):  
María Antonia Sánchez-Romero ◽  
Stephen J. W. Busby ◽  
Nigel P. Dyer ◽  
Sascha Ott ◽  
Andrew D. Millard ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Dna Microarrays ◽  
Nucleotide Metabolism ◽  
Entire Genome ◽  
Content Type ◽  
Genome Wide ◽  
Genes Encoding ◽  
K 12

ABSTRACTThe bacterial SeqA protein binds to hemi-methylated GATC sequences that arise in newly synthesized DNA upon passage of the replication machinery. InEscherichia coliK-12, the single replication originoriCis a well-characterized target for SeqA, which binds to multiple hemi-methylated GATC sequences immediately after replication has initiated. This sequestersoriC, thereby preventing reinitiation of replication. However, the genome-wide DNA binding properties of SeqA are unknown, and hence, here, we describe a study of the binding of SeqA across the entireEscherichia coliK-12 chromosome, using chromatin immunoprecipitation in combination with DNA microarrays. Our data show that SeqA binding correlates with the frequency and spacing of GATC sequences across the entire genome. Less SeqA is found in highly transcribed regions, as well as in thetermacrodomain. Using synchronized cultures, we show that SeqA distribution differs with the cell cycle. SeqA remains bound to some targets after replication has ceased, and these targets locate to genes encoding factors involved in nucleotide metabolism, chromosome replication, and methyl transfer.IMPORTANCEDNA replication in bacteria is a highly regulated process. In many bacteria, a protein called SeqA plays a key role by binding to newly replicated DNA. Thus, at the origin of DNA replication, SeqA binding blocks premature reinitiation of replication rounds. Although most investigators have focused on the role of SeqA at replication origins, it has long been suspected that SeqA has a more pervasive role. In this study, we describe how we have been able to identify scores of targets, across the entireEscherichia colichromosome, to which SeqA binds. Using synchronously growing cells, we show that the distribution of SeqA between these targets alters as replication of the chromosome progresses. This suggests that sequential changes in SeqA distribution orchestrate a program of gene expression that ensures coordinated DNA replication and cell division.

scholarly journals A conserved regulator controls asexual sporulation in the fungal pathogen Candida albicans

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Arturo Hernández-Cervantes ◽  
Sadri Znaidi ◽  
Lasse van Wijlick ◽  
Iryna Denega ◽  
Virginia Basso ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Chromatin Immunoprecipitation ◽  
Fungal Pathogen ◽  
Hyphal Growth ◽  
Second Phase ◽  
Asexual Sporulation ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Genome Wide Expression

AbstractTranscription factor Rme1 is conserved among ascomycetes and regulates meiosis and pseudohyphal growth in Saccharomyces cerevisiae. The genome of the meiosis-defective pathogen Candida albicans encodes an Rme1 homolog that is part of a transcriptional circuitry controlling hyphal growth. Here, we use chromatin immunoprecipitation and genome-wide expression analyses to study a possible role of Rme1 in C. albicans morphogenesis. We find that Rme1 binds upstream and activates the expression of genes that are upregulated during chlamydosporulation, an asexual process leading to formation of large, spherical, thick-walled cells during nutrient starvation. RME1 deletion abolishes chlamydosporulation in three Candida species, whereas its overexpression bypasses the requirement for chlamydosporulation cues and regulators. RME1 expression levels correlate with chlamydosporulation efficiency across clinical isolates. Interestingly, RME1 displays a biphasic pattern of expression, with a first phase independent of Rme1 function and dependent on chlamydospore-inducing cues, and a second phase dependent on Rme1 function and independent of chlamydospore-inducing cues. Our results indicate that Rme1 plays a central role in chlamydospore development in Candida species.

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