scholarly journals Role of transcription factor-mediated nucleosome disassembly in PHO5 gene expression

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hungyo Kharerin ◽  
Paike J. Bhat ◽  
John F. Marko ◽  
Ranjith Padinhateeri
Keyword(s):  
Gene Expression ◽  
Computational Study ◽  
Promoter Regions ◽  
Long Tail ◽  
Nucleosome Dynamics ◽  
Sequence Effects ◽  
Nucleosome Disassembly ◽  
Open Question ◽  
Kinetics Of

Abstract Studying nucleosome dynamics in promoter regions is crucial for understanding gene regulation. Nucleosomes regulate gene expression by sterically occluding transcription factors (TFs) and other non–histone proteins accessing genomic DNA. How the binding competition between nucleosomes and TFs leads to transcriptionally compatible promoter states is an open question. Here, we present a computational study of the nucleosome dynamics and organization in the promoter region of PHO5 gene in Saccharomyces cerevisiae. Introducing a model for nucleosome kinetics that takes into account ATP-dependent remodeling activity, DNA sequence effects and kinetics of TFs (Pho4p), we compute the probability of obtaining different “promoter states” having different nucleosome configurations. Comparing our results with experimental data, we argue that the presence of local remodeling activity (LRA) as opposed to basal remodeling activity (BRA) is crucial in determining transcriptionally active promoter states. By modulating the LRA and Pho4p binding rate, we obtain different mRNA distributions—Poisson, bimodal and long-tail. Through this work we explain many features of the PHO5 promoter such as sequence-dependent TF accessibility and the role of correlated dynamics between nucleosomes and TFs in opening/coverage of the TATA box. We also obtain possible ranges for TF binding rates and the magnitude of LRA.

scholarly journals Arabidopsis FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Krzysztof Brzezinka ◽  
Simone Altmann ◽  
Hjördis Czesnick ◽  
Philippe Nicolas ◽  
Michal Gorka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Nucleosome Occupancy ◽  
Promoter Regions ◽  
Nucleosome Remodeling ◽  
Chromatin Remodelers ◽  
Stress Memory ◽  
Active Memory ◽  
Nucleosome Dynamics ◽  
Sessile Organisms

Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the FORGETTER1 (FGT1) locus, with fgt1 mutants displaying reduced maintenance of heat-induced gene expression. FGT1 encodes the Arabidopsis thaliana orthologue of Strawberry notch (Sno), and the protein globally associates with the promoter regions of actively expressed genes in a heat-dependent fashion. FGT1 interacts with chromatin remodelers of the SWI/SNF and ISWI families, which also display reduced heat stress memory. Genomic targets of the BRM remodeler overlap significantly with FGT1 targets. Accordingly, nucleosome dynamics at loci with altered maintenance of heat-induced expression are affected in fgt1. Together, our results suggest that by modulating nucleosome occupancy, FGT1 mediates stress-induced chromatin memory.

ChIP-on-Chip Analysis Identified HLXB9 as a Transcription Factor In Hematopoietic Cells and Alters the Expression of Genes Involved In Cell-Adhesion

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2486-2486
Author(s):  
Sarah Wildenhain ◽  
Christian Ruckert ◽  
Svenja Daschkey ◽  
Martin Dugas ◽  
Julia Hauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Adhesion ◽  
Hematopoietic Cells ◽  
Promoter Regions ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
On Chip ◽  
Chip Analysis

Abstract Abstract 2486 Infants with t (7;12)/HLXB9-TEL positive Acute Myeloid Leukemia (AML) have an Event-Free Survival (EFS) of 0 % and are characterized by concomitant HLXB9 (MNX1) expression. However, the role of the homeobox protein HLXB9 on hematopoietic cell development remains unknown. Expression profiling of t (7;12) and t (11;X) positive leukemias revealed up-regulation of cell-cell interacting genes in t (7;12) positive leukemia (Wildenhain et al., 2010). Furthermore, no increased expression of HOX-Genes, like HOXA9 and MEIS1, could be observed in t (7;12) positive leukemia compared to t (11;X) positive leukemia. Based on the altered gene expression profile in t (7;12) positive leukemia we investigated the role of HLXB9 as a transcription factor in hematopoietic cells using ChIP-on-chip analysis and its impact on the cellular gene expression pattern using Affymetrix expression arrays. The myeloid cell line HL60 was stable transfected with a CMV-HLXB9 (HL60/HLXB9) expression vector or an empty vector control (HL60/control). Microarray analysis was performed using “Human Gene 1.0 ST Arrays” (Affymetrix) and data from the HL60/HLXB9 cells were normalized to HL60/control cells. ChIP-on-chip analysis was performed using the “SimpleChIP Enzymatic Chromatin IP Kit” (Cell Signaling Technologies). Hybridisation on “385K RefSeq Promoter arrays” and analysis of raw data were performed by NimbleGen using the NimbleScan software. Data were visualized with the SignalMap software. Altered expression analyses as well as enrichment of promoter regions were validated by quantitative RT-PCR. Expression analysis revealed 81 differentially expressed genes, whereof 63 were down-regulated indicating that HLXB9 acts as a transcriptional repressor, as characteristic for homeobox proteins. CLEC5A, normally expressed in mature myeloid cells, is the highest differentially repressed gene. Further, we identified several differentially expressed genes which interfere in cell-adhesion and/or angiogenesis (e.g. IL8, ZYX, SELL, SPP1, EMILIN2). Western blot analysis of nuclear extracts confirmed the translocation of HLXB9 into the nucleus. ChIP-on-chip analysis revealed binding of HLXB9 to several promoter regions, among them the promoters of ZYX and IL8. Binding of HLXB9 to those promoters results in a decreased gene expression.These data strengthens the hypothesis, that HLXB9 plays a major role in cell adhesion and/or cell interactions. Further we observed increased expression of the adhesion molecule CD11b, when culturing HL60/HLXB9 cells in All-Trans Retinoic Acid (ATRA) containing medium in contrast to HL60/control cells. In summary, this study shows that HLXB9 acts as a transcription factor in hematopoietic cells and has a repressive function on gene expression. HLXB9 target genes regulate cell-adhesion and angiogenesis. This study provides the first molecular results of HLXB9 function in hematopoietic cells and supports the previously published data showing the importance on altered gene expression of cell-cell interacting genes in the pathogenesis of t (7;12) positive leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hippocampal Gene Expression of Deiodinases 2 and 3 and Effects of 3,5-Diiodo-L-Thyronine T2 in Mouse Depression Paradigms

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Natalyia Markova ◽  
Anton Chernopiatko ◽  
Careen A. Schroeter ◽  
Dmitry Malin ◽  
Aslan Kubatiev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Antidepressant Treatment ◽  
Tail Suspension Test ◽  
Separate Experiment ◽  
Bolus Administration ◽  
Hormone Regulation ◽  
Inactive Metabolite ◽  
Kinetics Of

Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3′,5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated.

scholarly journals In Silico Prediction of Transcription Factor Collaborations Underlying Phenotypic Sexual Dimorphism in Zebrafish (Danio rerio)

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 873
Author(s):  
Shahrbanou Hosseini ◽  
Armin Otto Schmitt ◽  
Jens Tetens ◽  
Bertram Brenig ◽  
Henner Simianer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Sexual Dimorphism ◽  
Sex Determination ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Colour Pattern ◽  
Promoter Regions ◽  
Dimorphic Gene Expression

The transcriptional regulation of gene expression in higher organisms is essential for different cellular and biological processes. These processes are controlled by transcription factors and their combinatorial interplay, which are crucial for complex genetic programs and transcriptional machinery. The regulation of sex-biased gene expression plays a major role in phenotypic sexual dimorphism in many species, causing dimorphic gene expression patterns between two different sexes. The role of transcription factor (TF) in gene regulatory mechanisms so far has not been studied for sex determination and sex-associated colour patterning in zebrafish with respect to phenotypic sexual dimorphism. To address this open biological issue, we applied bioinformatics approaches for identifying the predicted TF pairs based on their binding sites for sex and colour genes in zebrafish. In this study, we identified 25 (e.g., STAT6-GATA4; JUN-GATA4; SOX9-JUN) and 14 (e.g., IRF-STAT6; SOX9-JUN; STAT6-GATA4) potentially cooperating TFs based on their binding patterns in promoter regions for sex determination and colour pattern genes in zebrafish, respectively. The comparison between identified TFs for sex and colour genes revealed several predicted TF pairs (e.g., STAT6-GATA4; JUN-SOX9) are common for both phenotypes, which may play a pivotal role in phenotypic sexual dimorphism in zebrafish.

scholarly journals The Clock Takes Shape—24 h Dynamics in Genome Topology

2022 ◽  
Vol 9 ◽  
Author(s):  
Kévin Tartour ◽  
Kiran Padmanabhan
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Metabolic Diseases ◽  
Cell Metabolism ◽  
Cellular Level ◽  
Damage Response ◽  
And Behavior ◽  
Open Question ◽  
Daily Changes

Circadian rhythms orchestrate organismal physiology and behavior in order to anticipate daily changes in the environment. Virtually all cells have an internal rhythm that is synchronized every day by Zeitgebers (environmental cues). The synchrony between clocks within the animal enables the fitness and the health of organisms. Conversely, disruption of rhythms is linked to a variety of disorders: aging, cancer, metabolic diseases, and psychological disorders among others. At the cellular level, mammalian circadian rhythms are built on several layers of complexity. The transcriptional-translational feedback loop (TTFL) was the first to be described in the 90s. Thereafter oscillations in epigenetic marks highlighted the role of chromatin state in organizing the TTFL. More recently, studies on the 3D organization of the genome suggest that genome topology could be yet another layer of control on cellular circadian rhythms. The dynamic nature of genome topology over a solar day implies that the 3D mammalian genome has to be considered in the fourth dimension-in time. Whether oscillations in genome topology are a consequence of 24 h gene-expression or a driver of transcriptional cycles remains an open question. All said and done, circadian clock-gated phenomena such as gene expression, DNA damage response, cell metabolism and animal behavior—go hand in hand with 24 h rhythms in genome topology.

scholarly journals RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis

2017 ◽  
Vol 214 (6) ◽  
pp. 1843-1855 ◽  
Author(s):  
Yan Xia ◽  
Weiwei Yang ◽  
Ming Fa ◽  
Xinjian Li ◽  
Yugang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Gene Expression Regulation ◽  
Chromatin Modification ◽  
Histone H3 ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Promoter Regions ◽  
Dependent Protein ◽  
Nucleosome Disassembly

Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2–phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription. RNF8-mediated histone H3 polyubiquitylation promotes tumor cell glycolysis and proliferation and brain tumorigenesis. Our findings uncover the role of RNF8-mediated histone H3 polyubiquitylation in the regulation of histone H3 stability and chromatin modification, paving the way to gene expression regulation and tumorigenesis.

scholarly journals Nucleosome assembly and disassembly pathways

2020 ◽  
Author(s):  
A. Hatakeyama ◽  
R. Retureau ◽  
M. Pasi ◽  
B. Hartmann ◽  
C. Nogues ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequence ◽  
Base Pair ◽  
Regulation Of Gene Expression ◽  
Detailed Comparison ◽  
Nucleosome Assembly ◽  
Nucleosome Dynamics ◽  
Intermediate States

AbstractNucleosome assembly and disassembly play a central role in the regulation of gene expression. Here we use PhAST (Photochemical Analysis of Structural Transitions) to monitor at the base pair level, structural alterations induced all along DNA upon histone binding or release. By offering the first consistent, detailed comparison of nucleosome assembly and disassembly in vitro, we are able to reveal similarities and differences between the two processes. We identify multiple intermediate states characterised by specific PhAST signatures; revealing a complexity that goes beyond the known sequential events involving (H3-H4)2 tetramer and H2A-H2B heterodimers. Such signatures localise and quantify the extent of the asymmetry of DNA/histone interactions with respect to the nucleosome dyad. This asymmetry is therefore defined by the localisation and amplitude of the signals. The localisation of the signal is consistent between assembly and disassembly and dictated by the DNA sequence. However, the amplitude component of this asymmetry not only evolves during the assembly and disassembly but does so differently between the two processes.Understanding the regulation of gene expression requires a complete knowledge of nucleosome dynamics. Our unexpected observation of differences between assembly and disassembly opens up new avenues to define the role of the DNA sequence in these processes. Overall, we provide new insights into how the intrinsic properties of DNA are integrated into a holistic mechanism that controls chromatin structure.Statement of SignificanceThis manuscript addresses the question of nucleosome dissociation compares with association. We used PhAST which is a non-intrusive photochemical technique to follow nucleosome dynamics at base pair resolution. We observed structural asymmetry during nucleosome turnover. We also showed for the first time that the process of nucleosome dissociation is not a reversal of association. This asymmetry favours intermediate states involved in chromatin organisation suggesting novel models for the role of nucleosome turnover in the epigenetic regulation of gene expression.

DNA methylation events in transcription factors and gene expression changes in colon cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 1593-1610
Author(s):  
Anna Díez-Villanueva ◽  
Rebeca Sanz-Pamplona ◽  
Robert Carreras-Torres ◽  
Ferran Moratalla-Navarro ◽  
M Henar Alonso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Colon Cancer ◽  
Transcription Factors ◽  
Target Genes ◽  
Linear Models ◽  
Cpg Islands ◽  
Promoter Regions ◽  
Differential Gene

Aim: Gain insight about the role of DNA methylation in the malignant growth of colon cancer. Patients & methods: Methylation and gene expression from 90 adjacent-tumor paired tissues and 48 healthy tissues were analyzed. Tumor genes whose change in expression was explained by changes in methylation were identified using linear models adjusted for tumor stromal content. Results: No differences in methylation were found between adjacent and healthy tissues, but clear differences were found between adjacent and tumor samples. We identified hypermethylated CpG islands located in promoter regions that drive differential gene expression of transcription factors and their target genes. Conclusion: Changes in methylation of a few genes provoke important changes in gene expression, by expanding the signal through transcription activation/repression.

scholarly journals The SWI/SNF and RSC Cooperatively Remodel the Promoters of Unfolded Protein Response Targets and Heat Shock Genes

2021 ◽  
Author(s):  
Rakesh Kumar Sahu ◽  
Sakshi Singh ◽  
Raghuvir Singh Tomar
Keyword(s):  
Gene Expression ◽  
Heat Shock ◽  
The Other ◽  
Epigenetic Factors ◽  
Promoter Regions ◽  
Chromatin Dynamics ◽  
Unfolded Protein ◽  
Or Gene ◽  
Protein Response

The ATP-dependent chromatin remodelling complexes maintain the chromatin dynamics, enabling the gene expression or its silencing. The SWI/SNF subfamily remodelers (SWI/SNF and RSC) generally promote gene expression by displacing or evicting nucleosomes at the promoter regions. Their action creates a nucleosome-depleted region where transcription machinery accesses the DNA. Their involvement has been shown critical for the induction of stress-responsive transcription programs. Although the role of SWI/SNF and RSC complexes in transcription regulation of heat shock responsive genes is well studied, their involvement at other pathway genes such as UPR, HSP and PQC is less known. In this study, we showed that the SWI/SNF occupies promoters of UPR, HSP and PQC genes in response to the unfolded protein stress, and its recruitment at UPR promoters is dependent on the Hac1 transcription factor and other epigenetic factors like Ada2 and Ume6. Disruption of SWI/SNF’s activity does not affect the remodelling of these promoters or gene expression. However, inactivation of both RSC and SWI/SNF complexes diminishes expression of most of the UPR, HSP and PQC genes tested. Altogether these results suggest that these two remodelers work together or one compensates the loss of the other to ensure optimal induction of the stress-responsive genes.

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