scholarly journals Hierarchical Domain Structure Reveals the Divergence of Activity among TADs and Boundaries

2018 ◽  
Author(s):  
Lin An ◽  
Tao Yang ◽  
Jiahao Yang ◽  
Johannes Nuebler ◽  
Guanjue Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Frequency ◽  
Spatial Organization ◽  
Running Speed ◽  
Structural Units ◽  
Regulatory Interactions ◽  
Topologically Associating Domains ◽  
Regulated Gene Expression ◽  
Improved Accuracy

AbstractThe spatial organization of chromatin in the nucleus has been implicated in many aspects of regulated gene expression. Maps of high frequency interactions between different segments of chromatin have revealed Topologically Associating Domains (TADs), within which most of the regulatory interactions are thought to occur. Recent studies have shown that TADs are not homogeneous structural units, but rather they appear to be organized into a hierarchy. However, precise identification of hierarchical TAD structures remains a challenge. We present OnTAD, an Optimized Nested TAD caller from Hi-C data, to identify hierarchical TADs. Compared to existing methods, OnTAD has significantly improved accuracy and running speed. Results from OnTAD reveal new biological insights on the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. The software and documentation for OnTAD are available at: https://github.com/anlin00007/OnTAD

scholarly journals OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lin An ◽  
Tao Yang ◽  
Jiahao Yang ◽  
Johannes Nuebler ◽  
Guanjue Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Domain Structure ◽  
High Frequency ◽  
Spatial Organization ◽  
Structural Units ◽  
Regulatory Interactions ◽  
Link Type ◽  
Topologically Associating Domains

AbstractThe spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed topologically associating domains (TADs), within which most of the regulatory interactions are thought to occur. TADs are not homogeneous structural units but appear to be organized into a hierarchy. We present OnTAD, an optimized nested TAD caller from Hi-C data, to identify hierarchical TADs. OnTAD reveals new biological insights into the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. OnTAD is available at https://github.com/anlin00007/OnTAD.

scholarly journals Role of a COP1 Interactive Protein in Mediating Light-Regulated Gene Expression in Arabidopsis

1998 ◽  
Vol 10 (7) ◽  
pp. 1083-1094 ◽  
Author(s):  
Yoshiharu Y. Yamamoto ◽  
Minami Matsui ◽  
Lay-Hong Ang ◽  
Xing-Wang Deng
Keyword(s):  
Gene Expression ◽  
Regulated Gene Expression

scholarly journals A gene regulatory motif that generates oscillatory or multiway switch outputs

2013 ◽  
Vol 10 (79) ◽  
pp. 20120826 ◽  
Author(s):  
Jasmina Panovska-Griffiths ◽  
Karen M. Page ◽  
James Briscoe
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Spatial Organization ◽  
Formation Mechanisms ◽  
Regulatory Interactions ◽  
Qualitative Dynamics ◽  
Gene Regulatory ◽  
Oscillatory Mechanisms ◽  
Parameter Values ◽  
Natural Way

The pattern of gene expression in a developing tissue determines the spatial organization of cell type generation. We previously defined regulatory interactions between a set of transcription factors that specify the pattern of gene expression in progenitors of different neuronal subtypes of the vertebrate neural tube. These transcription factors form a circuit that acts as a multistate switch, patterning the tissue in response to a gradient of Sonic Hedgehog. Here, by simplifying aspects of the regulatory interactions, we found that the topology of the circuit allows either switch-like or oscillatory behaviour depending on parameter values. The qualitative dynamics appear to be controlled by a simpler sub-circuit, which we term the AC–DC motif. We argue that its topology provides a natural way to implement a multistate gene expression switch and we show that the circuit is readily extendable to produce more distinct stripes of gene expression. Our analysis also suggests that AC–DC motifs could be deployed in tissues patterned by oscillatory mechanisms, thus blurring the distinction between pattern-formation mechanisms relying on temporal oscillations or graded signals. Furthermore, during evolution, mechanisms of gradient interpretation might have arisen from oscillatory circuits, or vice versa.

scholarly journals Role of metadherin in estrogen-regulated gene expression

2017 ◽  
Vol 40 (2) ◽  
pp. 303-310
Author(s):  
Yujun Li ◽  
Jesus Gonzalez Bosquet ◽  
Shujie Yang ◽  
Kristina W. Thiel ◽  
Yuping Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulated Gene Expression

scholarly journals Role of Nuclear Factor-κB in the Antiviral Action of Interferon and Interferon-regulated Gene Expression

2004 ◽  
Vol 279 (30) ◽  
pp. 31304-31311 ◽  
Author(s):  
Lawrence M. Pfeffer ◽  
Jong-Gwan Kim ◽  
Susan R. Pfeffer ◽  
Dennis J. Carrigan ◽  
Darren P. Baker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Antiviral Action ◽  
Regulated Gene Expression

scholarly journals An Improved Method for the Study of Apoptosis-Related Genes Using the Tet-On System

2011 ◽  
Vol 16 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Marc W. Halterman
Keyword(s):  
Gene Expression ◽  
Caspase 3 ◽  
Functional Characterization ◽  
Continuous Exposure ◽  
Genetic Screens ◽  
Pulse Dose ◽  
Target Effect ◽  
Regulated Gene Expression

Inducible gene expression systems are particularly useful for the functional characterization of genes with putative toxic properties. In the course of studying the role of hypoxia-regulated gene expression on cell survival using the tetracycline-inducible (tet-on) system, the author noted that exposure to the inducing ligand doxycycline (dox) inhibited caspase-3 cleavage in control samples. To limit this confounding off-target effect, he devised an in vitro pulse dose, delayed-injury protocol testing both dox and a novel tetracycline analog 9-t-butyl doxycycline (9-TB). Although 9-TB induced higher transgene levels compared to matched concentrations of dox, continuous exposure to both drugs inhibited caspase-3 cleavage in hypoxic samples. Conversely, a 6-h pulse dose of 9-TB followed by a 40-h washout period prior to hypoxic challenge activated robust transgene expression and lessened the inhibitory effects on caspase-3 processing. It is anticipated that these protocol modifications will improve the performance of tet-regulated genetic screens, particularly in situations where cell death is used as a primary end point.

scholarly journals A toxin-antitoxin system associated transcription factor of Caulobacter crescentus can influence cell cycle-regulated gene expression during the SOS response

2020 ◽  
Author(s):  
Koyel Ghosh ◽  
Kamilla Ankær Brejndal ◽  
Clare L. Kirkpatrick
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Damage ◽  
Transcription Factor ◽  
Caulobacter Crescentus ◽  
Sos Response ◽  
Cell Cycle Gene ◽  
Regulated Gene Expression ◽  
Cell Cycle Gene Expression

AbstractToxin-antitoxin (TA) systems are widespread in bacterial chromosomes but their functions remain enigmatic. Although many are transcriptionally upregulated by stress conditions, it is unclear what role they play in cellular responses to stress and to what extent the role of a given TA system homologue varies between different bacterial species. In this work we investigate the role of the DNA damage-inducible TA system HigBA of Caulobacter crescentus in the SOS response and discover that in addition to the toxin HigB affecting cell cycle gene expression through inhibition of the master regulator CtrA, HigBA possesses a transcription factor third component, HigC, which both auto-regulates the TA system and acts independently of it. Through HigC, the system exerts downstream effects on antibiotic (ciprofloxacin) resistance and cell cycle gene expression. HigB and HigC had inverse effects on cell cycle gene regulation, with HigB reducing and HigC increasing the expression of CtrA-dependent promoters. Neither HigBA nor HigC had any effect on formation of persister cells in response to ciprofloxacin. Rather, their role in the SOS response appears to be as transcriptional and post-transcriptional regulators of cell cycle-dependent gene expression, transmitting the status of the SOS response as a regulatory input into the cell cycle control network via CtrA.ImportanceAlmost all bacteria respond to DNA damage by upregulating a set of genes that helps them to repair and recover from the damage, known as the SOS response. The set of genes induced during the SOS response varies between species, but frequently includes toxin-antitoxin systems. However, it is unknown what the consequence of inducing these systems is, and whether they provide any benefit to the cells. We show here that the DNA damage-induced TA system HigBA of the asymmetrically dividing bacterium Caulobacter crescentus affects the cell cycle regulation of this bacterium. HigBA also has a transcription factor encoded immediately downstream of it, named here HigC, which controls expression of the TA system and potentially other genes as well. Therefore, this work identifies a new role for TA systems in the DNA damage response, distinct from non-specific stress tolerance mechanisms which had been proposed previously.

scholarly journals Cilium Expression Score Predicts Glioma Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Srinivas Rajagopalan ◽  
Amartya Singh ◽  
Hossein Khiabanian
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Poor Survival ◽  
Aggressive Tumors ◽  
Regulated Gene Expression ◽  
Upregulated Genes ◽  
Expression Score

The accurate classification, prognostication, and treatment of gliomas has been hindered by an existing cellular, genomic, and transcriptomic heterogeneity within individual tumors and their microenvironments. Traditional clustering is limited in its ability to distinguish heterogeneity in gliomas because the clusters are required to be exclusive and exhaustive. In contrast, biclustering can identify groups of co-regulated genes with respect to a subset of samples and vice versa. In this study, we analyzed 1,798 normal and tumor brain samples using an unsupervised biclustering approach. We identified co-regulated gene expression profiles that were linked to proximally located brain regions and detected upregulated genes in subsets of gliomas, associated with their histologic grade and clinical outcome. In particular, we present a cilium-associated signature that when upregulated in tumors is predictive of poor survival. We also introduce a risk score based on expression of 12 cilium-associated genes which is reproducibly informative of survival independent of other prognostic biomarkers. These results highlight the role of cilia in development and progression of gliomas and suggest potential therapeutic vulnerabilities for these highly aggressive tumors.

scholarly journals The role of insulators and transcription in 3D chromatin organisation of flies

2021 ◽  
Author(s):  
Keerthi T Chathoth ◽  
Liudmila A Mikheeva ◽  
Gilles Crevel ◽  
Jareth C. Wolfe ◽  
Ioni Hunter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Functional Role ◽  
Transcriptomic Data ◽  
Chromatin Loops ◽  
Topologically Associating Domains ◽  
Architectural Proteins ◽  
Chromatin Organisation

AbstractThe DNA in many organisms, including humans, is shown to be organised in topologically associating domains (TADs). InDrosophila, several architectural proteins are enriched at TAD borders, but it is still unclear whether these proteins play a functional role in the formation and maintenance of TADs. Here, we show that depletion of BEAF-32, Cp190, Chro and Dref leads to changes in TAD organisation and chromatin loops. Their depletion predominantly affects TAD borders located in heterochromatin, while TAD borders located in euchromatin are resilient to these mutants. Furthermore, transcriptomic data has revealed hundreds of genes displaying differential expression in these mutants and showed that the majority of differentially expressed genes are located within reorganised TADs. Our work identifies a novel and functional role for architectural proteins at TAD borders inDrosophilaand a link between TAD reorganisation and subsequent changes in gene expression.

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