scholarly journals Using ChIP-chip and ChIP-seq to study the regulation of gene expression: Genome-wide localization studies reveal widespread regulation of transcription elongation

Methods ◽  
2009 ◽  
Vol 48 (4) ◽  
pp. 398-408 ◽  
Author(s):  
Daniel A. Gilchrist ◽  
David C. Fargo ◽  
Karen Adelman
Keyword(s):  
Gene Expression ◽  
Transcription Elongation ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Genome Wide ◽  
Chip Chip

Linking transcription, RNA polymerase II elongation and alternative splicing

2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Polymerase Ii ◽  
Environmental Changes ◽  
Transcription Elongation ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Stepping Stones ◽  
Eukaryotic Transcription

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.

scholarly journals Genome-wide H3K9 Acetylation Level Increases with Age-Dependent Senescence of Flag Leaf in Rice (Oryza sativa)

2021 ◽  
Author(s):  
Yu Zhang ◽  
Yanyun Li ◽  
Yuanyuan Zhang ◽  
Zeyu Zhang ◽  
Deyu Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oryza Sativa ◽  
Leaf Senescence ◽  
Epigenetic Modification ◽  
Flag Leaf ◽  
Regulation Of Gene Expression ◽  
Leaf Aging ◽  
Genome Wide ◽  
Age Dependent ◽  
H3k9 Acetylation

Flag leaf senescence is an important biological process that drives the remobilization of nutrients to the growing organs of rice. Leaf senescence is controlled by genetic information via gene expression and epigenetic modification, but the precise mechanism is as of yet unclear. Here, we analyzed genome-wide acetylated lysine residue 9 of histone H3 (H3K9ac) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq) and examined its association with transcriptomes by RNA-seq during flag leaf aging in rice (Oryza sativa). We found that genome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and there was a positive correlation between the density and breadth of H3K9ac and gene expression and transcript elongation. A set of 1,249 up-regulated, differentially expressed genes (DEGs) and 996 down-regulated DEGs showing a strong relationship between temporal changes in gene expression and gain/loss of H3K9ac was observed during rice flag leaf aging. We produced a landscape of H3K9 acetylation- modified gene expression targets that includes known senescence-associated genes, metabolism-related genes, as well as miRNA biosynthesis- related genes. Our findings reveal a complex regulatory network of metabolism- and senescence-related pathways mediated by H3K9ac and also elucidate patterns of H3K9ac-mediated regulation of gene expression during flag leaf aging in rice.

GFI1b As a Novel Oncosuppressor in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2717-2717 ◽  
Author(s):  
Aniththa Thivakaran ◽  
Lacramioara Botezatu ◽  
Judith Maria Hoenes ◽  
Yahya Saleh Al-Matary ◽  
Nadine Olberding ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Molecular Level ◽  
Regulation Of Gene Expression ◽  
Leukemic Cells ◽  
Hematopoietic Stem ◽  
Genome Wide ◽  
Blast Cells ◽  
Leukemia Development

Abstract The proper differentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different so called transcription factors (TFs). A disturbed function of these TFs can be the basis of malignant diseases such as acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Growth Factor Independence 1b (Gfi1b) is a repressing transcription factor, with a key role in maintaining the quiescence of HSCs and the proper emergence and maturation of erythrocytes and platelets. Here we show that low expression of GFI1B in blast cells is associated with an inferior prognosis of AML and MDS patients. Using three different mice models of human AML (Nup98-HoxD13, MLL-AF9 and expression of a mutated K-Ras), we could show that reduced expression of Gfi1b accelerates AML development in mice and the latency is even more shortened when Gfi1b is conditionally deleted. Using a limiting dilution assay of transplantation of different number of Gfi1b-wildtype and Gfi1b-deficient cells, we could show that loss of Gfi1b significantly enhanced stemness of leukemic cells. Since Gfii1b is involved in epigenetic regulation of gene expression, we analyzed effect of loss of Gfi1b on an epigenetic level by analyzing the whole genome using Chip-Seq. We found that loss of Gfi1b leads to genome wide increased level of H3K9 acetylation of genes and hence expression of these genes involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increases the levels of reactive oxygen species (ROS), but also induces gene expression changes of key AML-pathways such as the p38/ AKT pathways. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development. Disclosures Dührsen: Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria, Research Funding. Khandanpour:Max-Eder: Research Funding; Hospital of Essen university: Research Funding.

scholarly journals The genome-wide role of HSF-1 in the regulation of gene expression in Caenorhabditis elegans

BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Jessica Brunquell ◽  
Stephanie Morris ◽  
Yin Lu ◽  
Feng Cheng ◽  
Sandy D. Westerheide
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Regulation Of Gene Expression ◽  
Genome Wide

scholarly journals Genome-Wide Gene Expression Analysis for Induced Ischemic Tolerance and Delayed Neuronal Death following Transient Global Ischemia in Rats

2004 ◽  
Vol 24 (2) ◽  
pp. 212-233 ◽  
Author(s):  
Nobutaka Kawahara ◽  
Yan Wang ◽  
Akitake Mukasa ◽  
Kazuhide Furuya ◽  
Tatsuya Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Neuronal Death ◽  
Gene Expression Analysis ◽  
Ischemic Tolerance ◽  
Global Ischemia ◽  
Delayed Neuronal Death ◽  
Regulation Of Transcription ◽  
Genome Wide ◽  
A Genome

enome-wide gene expression analysis of the hippocampal CA1 region was conducted in a rat global ischemia model for delayed neuronal death and induced ischemic tolerance using an oligonucleotide-based DNA microarray containing 8,799 probes. The results showed that expression levels of 246 transcripts were increased and 213 were decreased following ischemia, corresponding to 5.1% of the represented probe sets. These changes were divided into seven expression clusters using hierarchical cluster analysis, each with distinct conditions and time-specific patterns. Ischemic tolerance was associated with transient up-regulation of transcription factors (c-Fos, JunB Egr-1, −2, −4, NGFI-B), Hsp70 and MAP kinase cascade-related genes (MKP-1), which are implicated cell survival. Delayed neuronal death exhibited complex long-lasting changes of expression, such as up-regulation of proapoptotic genes (GADD153, Smad2, Dral, Caspase-2 and −3) and down-regulation of genes implicated in survival signaling (MKK2, and PI4 kinase, DAG/PKC signaling pathways), suggesting an imbalance between death and survival signals. Our study provides a differential gene expression profile between delayed neuronal death and induced ischemic tolerance in a genome-wide analysis, and contributes to further understanding of the complex molecular pathophysiology in cerebral ischemia.

scholarly journals Multivariable regulation of gene expression plasticity in metazoans

2019 ◽  
Author(s):  
Long Xiao ◽  
Zhiguang Zhao ◽  
Fei He ◽  
Zhuo Du
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Regulation Of Gene Expression ◽  
Rapid Change ◽  
High Plasticity ◽  
Expression Levels ◽  
Genome Wide ◽  
Expression Potential ◽  
Highly Correlated

ABSTRACTAn important capacity of genes is the rapid change of expression levels to cope with environment, known as expression plasticity. Elucidating the genomic mechanisms determining expression plasticity is critical for understanding the molecular basis of phenotypic plasticity, fitness, and adaptation. In this study, we systematically quantified genome-wide gene expression plasticity in four metazoan species by integrating changes of expression levels under a large number of genetic and environmental conditions. From this, we demonstrated that expression plasticity measures a distinct feature of gene expression that is orthogonal to other well-studies features including gene expression potential and tissue specificity/broadness. Expression plasticity is conserved across species with important physiological implications. The magnitude of expression plasticity is highly correlated with gene function and genes with high plasticity are implicated in disease susceptibility. Genome-wide analysis identified many conserved promoter cis-elements, trans-acting factors (such as CFCF), and gene body histone modifications (H3K36me3, H3K79me2, and H4K20me1) that are significantly associated with expression plasticity. Analysis of expression changes in perturbation experiments further validated a causal role of specific transcription factors and histone modifications. Collectively, this work reveals general properties, physiological implications, and multivariable regulation of gene expression plasticity in metazoans, extending the mechanistic understanding of gene regulation.

scholarly journals Chromatin-associated protein complexes link DNA base J and transcription termination in Leishmania

2020 ◽  
Author(s):  
Bryan C Jensen ◽  
Isabelle Q. Phan ◽  
Jacquelyn R. McDonald ◽  
Aakash Sur ◽  
Mark A. Gillespie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Protein Complexes ◽  
Transcription Termination ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Control Of Gene Expression ◽  
Polycistronic Transcription ◽  
Post Transcriptional Regulation

AbstractUnlike most other eukaryotes, Leishmania and other trypanosomatid protozoa have largely eschewed transcriptional control of gene expression; relying instead on post-transcriptional regulation of mRNAs derived from polycistronic transcription units (PTUs). In these parasites, a novel modified nucleotide base (β-D-glucopyranosyloxymethyluracil) known as J plays a critical role in ensuring that transcription termination occurs only at the end of each PTU, rather than at the polyadenylation sites of individual genes. To further understand the biology of J-associated processes, we used tandem affinity purification (TAP-tagging) and mass spectrometry to reveal proteins that interact with the glucosyltransferase performing the final step in J synthesis. These studies identified four proteins reminiscent of subunits in the PTW/PP1 complex that controls transcription termination in higher eukaryotes. Moreover, bioinformatic analyses identified the DNA-binding subunit of Leishmania PTW/PP1 as a novel J-binding protein (JBP3). Down-regulation of JBP3 expression levels in Leishmania resulted in a substantial increase in transcriptional read-through at the 3’ end of most PTUs. Additional TAP-tagging experiments showed that JBP3 also associates with two other protein complexes. One consists of subunits with domains suggestive of a role in chromatin modification/remodeling; while the other contains subunits with similarity to those found in the PAF1 complex involved in regulation of transcription in other eukaryotes. Thus, trypanosomatids utilize protein complexes similar to those used to control transcription termination in other eukaryotes and JBP3 appears to function as a hub linking these modules to base J, thereby enabling the parasites’ unique reliance on polycistronic transcription and post-transcriptional regulation of gene expression.

scholarly journals Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Sanket Nagarkar ◽  
Ruchi Wasnik ◽  
Pravallika Govada ◽  
Stephen Cohen ◽  
L. S. Shashidhara
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Elongation Factor ◽  
Imaginal Discs ◽  
Link Type ◽  
Genome Wide ◽  
Wing Imaginal Discs ◽  
Tumorous Growth

Promoter proximal pausing (PPP) of RNA polymerase II has emerged as a crucial rate-limiting step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT), and the negative elongation factor (NELF), which are highly conserved from Drosophila to humans. Here, we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhances Yki-driven growth, leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki in driving neoplastic growth. Interestingly, overexpression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily, and specifically, needed Yki overexpression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP—the ortholog of Yki in humans.

scholarly journals Gene Architecture Facilitates Intron-Mediated Enhancement of Transcription

2021 ◽  
Vol 8 ◽  
Author(s):  
Katherine Dwyer ◽  
Neha Agarwal ◽  
Lori Pile ◽  
Athar Ansari
Keyword(s):  
Gene Expression ◽  
Splice Site ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Initiation Of Transcription ◽  
Gene Architecture ◽  
Mammalian Genes ◽  
Higher Eukaryotes ◽  
Eukaryotic Organisms

Introns impact several vital aspects of eukaryotic organisms like proteomic plasticity, genomic stability, stress response and gene expression. A role for introns in the regulation of gene expression at the level of transcription has been known for more than thirty years. The molecular basis underlying the phenomenon, however, is still not entirely clear. An important clue came from studies performed in budding yeast that indicate that the presence of an intron within a gene results in formation of a multi-looped gene architecture. When looping is defective, these interactions are abolished, and there is no enhancement of transcription despite normal splicing. In this review, we highlight several potential mechanisms through which looping interactions may enhance transcription. The promoter-5′ splice site interaction can facilitate initiation of transcription, the terminator-3′ splice site interaction can enable efficient termination of transcription, while the promoter-terminator interaction can enhance promoter directionality and expedite reinitiation of transcription. Like yeast, mammalian genes also exhibit an intragenic interaction of the promoter with the gene body, especially exons. Such promoter-exon interactions may be responsible for splicing-dependent transcriptional regulation. Thus, the splicing-facilitated changes in gene architecture may play a critical role in regulation of transcription in yeast as well as in higher eukaryotes.

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