scholarly journals Mammalian Ssu72 phosphatase preferentially considers tissue-specific actively transcribed gene expression by regulating RNA Pol II transcription

Theranostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 186-206
Author(s):  
Hyun-Soo Kim ◽  
Yoon Jeon ◽  
Yoon Ok Jang ◽  
Ho Lee ◽  
Yong Shin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Tissue Specific

scholarly journals In situ dissection of domain boundaries affect genome topology and gene transcription in Drosophila

2019 ◽  
Author(s):  
Rodrigo G. Arzate-Mejía ◽  
Angel Josué Cerecedo-Castillo ◽  
Georgina Guerrero ◽  
Mayra Furlan-Magaril ◽  
Félix Recillas-Targa
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Topological Defects ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Domain Boundaries ◽  
Topologically Associated Domains ◽  
Genetic Sequences

AbstractThe molecular mechanisms responsible for Topologically Associated Domains (TADs) formation are not yet fully understood. In Drosophila, it has been proposed that transcription is fundamental for TAD organization while the participation of genetic sequences bound by Architectural Proteins (APs) remains controversial. Here, we investigate the contribution of domain boundaries to TAD organization and the regulation of gene expression at the Notch gene locus in Drosophila. We find that deletion of domain boundaries results in TAD fusion and long-range topological defects that are accompanied by loss of APs and RNA Pol II chromatin binding as well as defects in transcription. Together, our results provide compelling evidence on the contribution of discrete genetic sequences bound by APs and RNA Pol II in the partition of the genome into TADs and in the regulation of gene expression in Drosophila.

scholarly journals Cohesin removal reprograms gene expression upon mitotic entry

2019 ◽  
Author(s):  
Carlos Perea-Resa ◽  
Leah Bury ◽  
Iain Cheeseman ◽  
Michael D. Blower
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Rna Polymerase Ii ◽  
Chromosome Segregation ◽  
List Type ◽  
Mitotic Chromosomes ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Mitotic Entry ◽  
Nascent Transcripts

SummaryEntering mitosis, the genome is restructured to facilitate chromosome segregation, accompanied by dramatic changes in gene expression. However, the mechanisms that underlie mitotic transcriptional regulation are unclear. In contrast to transcribed genes, centromere regions retain transcriptionally active RNA Polymerase II (RNAPII) in mitosis. Here, we demonstrate that chromatin-bound cohesin is sufficient to retain RNAPII at centromeres while WAPL-mediated removal of cohesin during prophase is required for RNAPII dissociation from chromosome arms. Failure to remove cohesin from chromosome arms results in a failure to release elongating RNAPII and nascent transcripts from mitotic chromosomes and dramatically alters gene expression. We propose that prophase cohesin removal is the key step in reprogramming gene expression as cells transition from G2 to mitosis, and is temporally coupled with chromosome condensation to coordinate chromosome segregation with changes in gene expression.HighlightsMitotic centromere transcription requires cohesinCohesin removal releases elongating RNA Pol II and nascent RNA from chromatinThe prophase pathway reprograms gene expression during mitosis

scholarly journals RNA Polymerase I Transcribes Procyclin Genes and Variant Surface Glycoprotein Gene Expression Sites in Trypanosoma brucei

2003 ◽  
Vol 2 (3) ◽  
pp. 542-551 ◽  
Author(s):  
Arthur Günzl ◽  
Thomas Bruderer ◽  
Gabriele Laufer ◽  
Bernd Schimanski ◽  
Lan-Chun Tu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Trypanosoma Brucei ◽  
Protein C ◽  
Gene Promoter ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Pol I

ABSTRACT In eukaryotes, RNA polymerase (pol) I exclusively transcribes the large rRNA gene unit (rDNA) and mRNA is synthesized by RNA pol II. The African trypanosome, Trypanosoma brucei, represents an exception to this rule. In this organism, transcription of genes encoding the variant surface glycoprotein (VSG) and the procyclins is resistant to α-amanitin, indicating that it is mediated by RNA pol I, while other protein-coding genes are transcribed by RNA pol II. To obtain firm proof for this concept, we generated a T. brucei cell line which exclusively expresses protein C epitope-tagged RNA pol I. Using an anti-protein C immunoaffinity matrix, we specifically depleted RNA pol I from transcriptionally active cell extracts. The depletion of RNA pol I impaired in vitro transcription initiated at the rDNA promoter, the GPEET procyclin gene promoter, and a VSG gene expression site promoter but did not affect transcription from the spliced leader (SL) RNA gene promoter. Fittingly, induction of RNA interference against the RNA pol I largest subunit in insect-form trypanosomes significantly reduced the relative transcriptional efficiency of rDNA, procyclin genes, and VSG expression sites in vivo whereas that of SL RNA, αβ-tubulin, and heat shock protein 70 genes was not affected. Our studies unequivocally show that T. brucei harbors a multifunctional RNA pol I which, in addition to transcribing rDNA, transcribes procyclin genes and VSG gene expression sites.

scholarly journals Cell-Type-Specific Profiling of Gene Expression and Chromatin Binding without Cell Isolation: Assaying RNA Pol II Occupancy in Neural Stem Cells

2013 ◽  
Vol 26 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Tony D. Southall ◽  
Katrina S. Gold ◽  
Boris Egger ◽  
Catherine M. Davidson ◽  
Elizabeth E. Caygill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Isolation ◽  
Chromatin Binding ◽  
Cell Type ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Cell Type Specific

scholarly journals Sequential Entry of Components of Gene Expression Machinery into Daughter Nuclei

2003 ◽  
Vol 14 (3) ◽  
pp. 1043-1057 ◽  
Author(s):  
Kannanganattu V. Prasanth ◽  
Paula A. Sacco-Bubulya ◽  
Supriya G. Prasanth ◽  
David L. Spector
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Splicing Factors ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
General Transcription Factors ◽  
Sequential Entry ◽  
Processing Factors

In eukaryotic cells, RNA polymerase II (RNA pol II) transcription and pre-mRNA processing are coordinated events. We have addressed how individual components of the transcription and pre-mRNA processing machinery are organized during mitosis and subsequently recruited into the newly formed daughter nuclei. Interestingly, localization studies of numerous RNA pol II transcription and pre-mRNA processing factors revealed a nonrandom and sequential entry of these factors into daughter nuclei after nuclear envelope/lamina formation. The initiation competent form of RNA pol II and general transcription factors appeared in the daughter nuclei simultaneously, but prior to pre-mRNA processing factors, whereas the elongation competent form of RNA pol II was detected even later. The differential entry of these factors rules out the possibility that they are transported as a unitary complex. Telophase nuclei were competent for transcription and pre-mRNA splicing concomitant with the initial entry of the respective factors. In addition, our results revealed a low turnover rate of transcription and pre-mRNA splicing factors during mitosis. We provide evidence to support a model in which the entry of the RNA pol II gene expression machinery into newly forming daughter nuclei is a staged and ordered process.

scholarly journals c-Myc Is Required for the ChREBP-Dependent Activation of Glucose-Responsive Genes

2010 ◽  
Vol 24 (6) ◽  
pp. 1274-1286 ◽  
Author(s):  
Pili Zhang ◽  
Mallikarjurna R. Metukuri ◽  
Sharell M. Bindom ◽  
Edward V. Prochownik ◽  
Robert M. O'Doherty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Time Course ◽  
Target Genes ◽  
Process Time ◽  
Glucose Response ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Molecular Events ◽  
Regulated Gene Expression

Abstract Glucose regulates programs of gene expression that orchestrate changes in cellular phenotype in several metabolically active tissues. Carbohydrate response element-binding protein (ChREBP) and its binding partner, Mlx, mediate glucose-regulated gene expression by binding to carbohydrate response elements on target genes, such as the prototypical glucose-responsive gene, liver-type pyruvate kinase (Pklr). c-Myc is also required for the glucose response of the Pklr gene, although the relationship between c-Myc and ChREBP has not been defined. Here we describe the molecular events of the glucose-mediated activation of Pklr and determine the effects of decreasing the activity or abundance of c-Myc on this process. Time-course chromatin immunoprecipitation revealed a set of transcription factors [hepatocyte nuclear factor (HNF)1α, HNF4α, and RNA polymerase II (Pol II)] constitutively resident on the Pklr promoter, with a relative enrichment of acetylated histones 3 and 4 in the same region of the gene. Glucose did not affect HNF1α binding or the acetylation of histones H3 or H4. By contrast, glucose promoted the recruitment of ChREBP and c-Myc and increased the occupancy of HNF4α and RNA Pol II, which were coincident with the glucose-mediated increase in transcription as determined by a nuclear run-on assay. Depletion of c-Myc activity using a small molecule inhibitor (10058-F4/1RH) abolished the glucose-mediated recruitment of HNF4α, ChREBP, and RNA Pol II, without affecting basal gene expression, histone acetylation, and HNF1α or basal HNF4α occupancy. The activation and recruitment of ChREBP to several glucose-responsive genes were blocked by 1RH, indicating a general necessity for c-Myc in this process.

scholarly journals Trypanosoma brucei ribonuclease H2A is an essential R-loop processing enzyme whose loss causes DNA damage during transcription initiation and antigenic variation

2019 ◽  
Vol 47 (17) ◽  
pp. 9180-9197 ◽  
Author(s):  
Emma Briggs ◽  
Kathryn Crouch ◽  
Leandro Lemgruber ◽  
Graham Hamilton ◽  
Craig Lapsley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Trypanosoma Brucei ◽  
Transcription Initiation ◽  
Critical Role ◽  
Rnase H ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Pol I ◽  
Rnase H2

Abstract Ribonucleotides represent a threat to DNA genome stability and transmission. Two types of Ribonuclease H (RNase H) excise ribonucleotides when they form part of the DNA strand, or hydrolyse RNA when it base-pairs with DNA in structures termed R-loops. Loss of either RNase H is lethal in mammals, whereas yeast survives the absence of both enzymes. RNase H1 loss is tolerated by the parasite Trypanosoma brucei but no work has examined the function of RNase H2. Here we show that loss of T. brucei RNase H2 (TbRH2A) leads to growth and cell cycle arrest that is concomitant with accumulation of nuclear damage at sites of RNA polymerase (Pol) II transcription initiation, revealing a novel and critical role for RNase H2. Differential gene expression analysis reveals limited overall changes in RNA levels for RNA Pol II genes after TbRH2A loss, but increased perturbation of nucleotide metabolic genes. Finally, we show that TbRH2A loss causes R-loop and DNA damage accumulation in telomeric RNA Pol I transcription sites, also leading to altered gene expression. Thus, we demonstrate separation of function between two nuclear T. brucei RNase H enzymes during RNA Pol II transcription, but overlap in function during RNA Pol I-mediated gene expression during host immune evasion.

scholarly journals Selective Requirement for SAGA in Hog1-Mediated Gene Expression Depending on the Severity of the External Osmostress Conditions

2007 ◽  
Vol 27 (11) ◽  
pp. 3900-3910 ◽  
Author(s):  
Meritxell Zapater ◽  
Marc Sohrmann ◽  
Matthias Peter ◽  
Francesc Posas ◽  
Eulàlia de Nadal
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Genetic Screening ◽  
Essential Role ◽  
Regulation Of Gene Expression ◽  
Transcriptional Program ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Genome Wide ◽  
Transcriptional Complex

ABSTRACT Regulation of gene expression by the Hog1 stress-activated protein kinase is essential for proper cell adaptation to osmostress. Hog1 coordinates an extensive transcriptional program through the modulation of transcription. To identify systematically novel components of the transcriptional machinery required for osmostress-mediated gene expression, we performed an exhaustive genome-wide genetic screening, searching for mutations that render cells osmosensitive at high osmolarity and that are associated with reduced expression of osmoresponsive genes. The SAGA and Mediator complexes were identified as putative novel regulators of osmostress-mediated transcription. Interestingly, whereas Mediator is essential for osmostress gene expression, the requirement for SAGA is different depending on the strength of the extracellular osmotic conditions. At mild osmolarity, SAGA mutants show only very slight defects on RNA polymerase II (Pol II) recruitment and gene expression, whereas at severe osmotic conditions, SAGA mutants show completely impaired RNA Pol II recruitment and transcription of osmoresponsive genes. Thus, our results define an essential role for Mediator in osmostress gene expression and a selective role for SAGA under severe osmostress. Our results indicate that the requirement for a transcriptional complex to regulate a promoter might be determined by the strength of the stimuli perceived by the cell through the regulation of interactions between transcriptional complexes.

scholarly journals Active Chromatin Hub of the Mouse α-Globin Locus Forms in a Transcription Factory of Clustered Housekeeping Genes

2006 ◽  
Vol 26 (13) ◽  
pp. 5096-5105 ◽  
Author(s):  
Guo-Ling Zhou ◽  
Li Xin ◽  
Wei Song ◽  
Li-Jun Di ◽  
Guang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Globin Gene ◽  
Housekeeping Genes ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Globin Genes ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Transcription Factory

ABSTRACT RNA polymerases can be shared by a particular group of genes in a transcription “factory” in nuclei, where transcription may be coordinated in concert with the distribution of coexpressed genes in higher-eukaryote genomes. Moreover, gene expression can be modulated by regulatory elements working over a long distance. Here, we compared the conformation of a 130-kb chromatin region containing the mouse α-globin cluster and their flanking housekeeping genes in 14.5-day-postcoitum fetal liver and brain cells. The analysis of chromatin conformation showed that the active α1 and α2 globin genes and upstream regulatory elements are in close spatial proximity, indicating that looping may function in the transcriptional regulation of the mouse α-globin cluster. In fetal liver cells, the active α1 and α2 genes, but not the inactive ζ gene, colocalize with neighboring housekeeping genes C16orf33, C16orf8, MPG, and C16orf35. This is in sharp contrast with the mouse α-globin genes in nonexpressing cells, which are separated from the congregated housekeeping genes. A comparison of RNA polymerase II (Pol II) occupancies showed that active α1 and α2 gene promoters have a much higher RNA Pol II enrichment in liver than in brain. The RNA Pol II occupancy at the ζ gene promoter, which is specifically repressed during development, is much lower than that at the α1 and α2 promoters. Thus, the mouse α-globin gene cluster may be regulated through moving in or out active globin gene promoters and regulatory elements of a preexisting transcription factory in the nucleus, which is maintained by the flanking clustered housekeeping genes, to activate or inactivate α-globin gene expression.

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