scholarly journals TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation

2018 ◽  
Author(s):  
Roberto Ferrari ◽  
Lara Isabel de Llobet Cucalon ◽  
Chiara Di Vona ◽  
François Le Dilly ◽  
Enrique Vidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Histone Acetylation ◽  
Cancer Biology ◽  
Repetitive Elements ◽  
Large Set ◽  
Alu Elements ◽  
Cell Cycle Genes ◽  
Chromatin Looping

Summary paragraphThe mammalian genome is shaped by the expansion of repetitive elements that provide new regulatory networks for coordinated control of gene expression1 and genome folding2–4. Alu elements (AEs) are selectively retained close to the transcription start site of genes5, show protoenhancer functions6, correlate with the level of chromatin interactions7 and are recognized by transcription factor III (TFIIIC)8, but the relevance of all this is not clear. Here we report regulatory mechanisms that unveil a central role of AEs and TFIIIC in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of pre-marked AEs near cell cycle genes recruit TFIIIC to alter their chromatin accessibility via TFIIIC-mediated acetylation of histone H3 Lysine-18 (H3K18). This facilitates AEs contact with distant CTCF sites near other cell cycle genes promoters, which also become hyperacetylated at H3K18. These changes ensure basal transcription of crucial cell cycle genes, and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor adjusts 3D genome folding and gene expression. We anticipate that expansion of several families of repetitive elements during evolution might have served to generate new genomic cis-regulatory circuits enabling the coordinated regulation of a large set of genes relevant for cellular stress survival. As growth factor withdrawal is a situation relevant in cancer biology, our study identifies TFIIIC as a new potential target for clinical intervention.

scholarly journals TFIIIC Binding to Alu Elements Controls Gene Expression via Chromatin Looping and Histone Acetylation

2020 ◽  
Vol 77 (3) ◽  
pp. 475-487.e11 ◽  
Author(s):  
Roberto Ferrari ◽  
Lara Isabel de Llobet Cucalon ◽  
Chiara Di Vona ◽  
François Le Dilly ◽  
Enrique Vidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Alu Elements ◽  
Chromatin Looping

scholarly journals Transcriptional landscape of cell lines and their tissues of origin

2016 ◽  
Author(s):  
Camila M. Lopes-Ramos ◽  
Joseph N. Paulson ◽  
Cho-Yi Chen ◽  
Marieke L. Kuijjer ◽  
Maud Fagny ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
List Type ◽  
Cell Cycle Genes ◽  
Barr Virus ◽  
Network Analyses ◽  
Regulatory Processes

SummaryCell lines are an indispensable tool in biomedical research and often used as surrogates for tissues. An important question is how well a cell line’s transcriptional and regulatory processes reflect those of its tissue of origin. We analyzed RNA-Seq data from GTEx for 127 paired Epstein-Barr virus transformed lymphoblastoid cell lines and whole blood samples; and 244 paired fibroblast cell lines and skin biopsies. A combination of gene expression and network analyses shows that while cell lines carry the expression signatures of their primary tissues, albeit at reduced levels, they also exhibit changes in their patterns of transcription factor regulation. Cell cycle genes are over-expressed in cell lines compared to primary tissue, and they have a reduction of repressive transcription factor targeting. Our results provide insight into the expression and regulatory alterations observed in cell lines and suggest that these changes should be considered when using cell lines as models.HighlightsCell lines differ from their source tissues in gene expression and regulationDistinct cell lines share altered patterns of cell cycle regulationCell cycle genes are less strongly targeted by repressive TFs in cell linesCell lines share expression with their source tissue, but at reduced levels

scholarly journals Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Prediction Models ◽  
Long Distance ◽  
Chromatin Looping ◽  
Gene Regulatory ◽  
The Impact

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

scholarly journals Registered report: Transcriptional amplification in tumor cells with elevated c-Myc

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
David Blum ◽  
Haiping Hao ◽  
Michael McCarthy ◽  
Keyword(s):  
Gene Expression ◽  
Tumor Cells ◽  
Cancer Biology ◽  
Cell Model ◽  
Scientific Research ◽  
Digital Gene Expression ◽  
Open Science ◽  
Large Set ◽  
Mrna Levels ◽  
Transcriptional Amplification

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Transcriptional amplification in tumor cells with elevated c-Myc’ by <xref ref-type="bibr" rid="bib5">Lin et al. (2012)</xref>, published in Cell in 2012. The experiments that will be replicated are those reported in Figures 3E and 3F. In these experiments, elevated levels of c-Myc in the P493-6 cell model of Burkitt's lymphoma results in an increase of the total level of RNA using UV/VIS spectrophotometry (Figure 3E; <xref ref-type="bibr" rid="bib5">Lin et al., 2012</xref>) and on the mRNA levels/cell for a large set of genes using digital gene expression technology (Figure 3F; <xref ref-type="bibr" rid="bib5">Lin et al., 2012</xref>). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published in eLife.

scholarly journals Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7035 ◽  
Author(s):  
Emmanuelle Deniaud ◽  
Joël Baguet ◽  
Roxane Chalard ◽  
Bariza Blanquier ◽  
Lilia Brinza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factor Sp1 ◽  
Cell Cycle Inhibition

Neighbourhoods in the yeast regulatory network in different physiological states

2020 ◽  
Author(s):  
Arthur M Lesk ◽  
Arun S Konagurthu
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Damage ◽  
Transcription Factor ◽  
Stress Response ◽  
Local Structure ◽  
Regulatory Network ◽  
Diauxic Shift ◽  
Central Node ◽  
Similarities And Differences

Abstract Motivation The gene expression regulatory network in yeast controls the selective implementation of the information contained in the genome sequence. We seek to understand how, in different physiological states, the network reconfigures itself to produce a different proteome. Results This article analyses this reconfiguration, focussing on changes in the local structure of the network. In particular, we define, extract and compare the 1-neighbourhoods of each transcription factor, where a 1-neighbourhood of a node in a network is the minimal subgraph of the network containing all nodes connected to the central node by an edge. We report the similarities and differences in the topologies and connectivities of these neighbourhoods in five physiological states for which data are available: cell cycle, DNA damage, stress response, diauxic shift and sporulation. Based on our analysis, it seems apt to regard the components of the regulatory network as ‘software’, and the responses to changes in state, ‘reprogramming’.

scholarly journals Dependence of transcriptional repression on CpG methylation density.

1994 ◽  
Vol 14 (8) ◽  
pp. 5487-5494 ◽  
Author(s):  
C L Hsieh
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Histone Acetylation ◽  
Chromatin Structure ◽  
Transcriptional Repression ◽  
Cpg Methylation ◽  
Dna Looping ◽  
Dynamic Features ◽  
Butyrate Treatment ◽  
Low Levels

CpG methylation is known to suppress transcription. This repression is generally thought to be related to alterations of chromatin structure that are specified by the methylation. The nature of these chromatin alterations is unknown. Moreover, it has not been clear if the methylation repression occurs in an all-or-none fashion at some critical methylation density, or if intermediate densities of methylation can give intermediate levels of repression. Here I report a stable episomal system which recapitulates many dynamic features of methylation observed in the genome. I have determined the extent of transcriptional repression as a function of four densities of CpG methylation. I find that the repression is a graded but exponential function of the CpG methylation density such that low levels of methylation yield a 67 to 90% inhibition of gene expression. Higher levels of methylation extinguished gene expression completely. Transcription from methylated minichromosomes can be increased by butyrate treatment, suggesting that histone acetylation can reverse some of the repression specified by the methylated state. Sites of preferential demethylation occurred and may have resulted from transcription factor binding or DNA looping.

scholarly journals Influence of fatty acid diets on gene expression in rat mammary epithelial cells

2009 ◽  
Vol 38 (1) ◽  
pp. 80-88 ◽  
Author(s):  
M. Medvedovic ◽  
R. Gear ◽  
J. M. Freudenberg ◽  
J. Schneider ◽  
R. Bornschein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Epithelial Cells ◽  
Differential Expression ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Cell Cycle Genes

Background: This study examines the impact of dietary fatty acids on regulation of gene expression in mammary epithelial cells before and during puberty. Methods: Diets primarily consisted of n-9 monounsaturated fatty acids (olive oil), n-6 polyunsaturated fatty acids (safflower), saturated acids (butter), and the reference AIN-93G diet (soy oil). The dietary regimen mimics the repetitive nature of fatty acid exposure in Western diets. Diet-induced changes in gene expression were examined in laser capture microdissected mammary ductal epithelial cells at day of weaning and end of puberty. PCNA immunohistochemistry analysis compared proliferation rates between diets. Results: Genes differentially expressed between each test diets and the reference diet were significantly enriched by cell cycle genes. Some of these genes were involved in activation of the cell cycle pathway or the G2/M check point pathway. Although there were some differences in the level of differential expression, all diets showed qualitatively the same pattern of differential expression compared to the reference diet. Cluster analysis identified an expanded set of cell cycle as well as immunity and sterol metabolism related clusters of differentially expressed genes. Conclusion: Fatty acid-enriched diets significantly upregulated proliferation above normal physiological levels during puberty. Higher cellular proliferation during puberty caused by enriched fatty acid diets poses a potential increase risk of mammary cancer in later life. The human homologs of 27 of 62 cell cycle rat genes are included in a human breast cancer cluster of 45 cell cycle genes, further emphasizing the importance of our findings in the rat model.

Sign in / Sign up

Export Citation Format

Share Document