scholarly journals Regulation of transcription reactivation dynamics exiting mitosis

2020 ◽  
Author(s):  
Sergio Sarnataro ◽  
Andrea Riba ◽  
Nacho Molina
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Control Cell ◽  
Core Gene ◽  
Regulation Of Transcription ◽  
Gene Regulatory

AbstractProliferating cells experience a global reduction of transcription during mitosis, yet their cell identity is maintained and regulatory information is propagated from mother to daughter cells. Mitotic bookmarking by transcription factors has been proposed as a potential mechanism to ensure the reactivation of transcription at the proper set of genes exiting mitosis. Recently, mitotic transcription and waves of transcription reactivation have been observed in synchronized populations of human hepatoma cells. However, the study did not consider that mitotic-arrested cell populations progressively desynchronize leading to measurements of gene expression on a mixture of cells at different internal cell-cycle times. Moreover, it is not well understood yet what is the precise role of mitotic bookmarking on mitotic transcription as well as on the transcription reactivation waves. Ultimately, the core gene regulatory network driving the precise transcription reactivation dynamics remains to be identified. To address these questions, we developed a mathematical model to correct for the progressive desynchronization of cells and estimate gene expression dynamics with respect to a cell-cycle pseudotime. Furthermore, we used a multiple linear regression model to infer transcription factor activity dynamics. Our analysis allows us to characterize waves of transcription factor activities exiting mitosis and identify a core gene regulatory network responsible of the transcription reactivation dynamics. Moreover, we identified more than 60 transcription factors that are highly active during mitosis and represent new candidates of mitotic bookmarking factors which could represent relevant therapeutic targets to control cell proliferation.

scholarly journals Regulation of transcription reactivation dynamics exiting mitosis

2021 ◽  
Vol 17 (10) ◽  
pp. e1009354
Author(s):  
Sergio Sarnataro ◽  
Andrea Riba ◽  
Nacho Molina
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Control Cell ◽  
Core Gene ◽  
Regulation Of Transcription ◽  
Gene Regulatory

Proliferating cells experience a global reduction of transcription during mitosis, yet their cell identity is maintained and regulatory information is propagated from mother to daughter cells. Mitotic bookmarking by transcription factors has been proposed as a potential mechanism to ensure the reactivation of transcription at the proper set of genes exiting mitosis. Recently, mitotic transcription and waves of transcription reactivation have been observed in synchronized populations of human hepatoma cells. However, the study did not consider that mitotic-arrested cell populations progressively desynchronize leading to measurements of gene expression on a mixture of cells at different internal cell-cycle times. Moreover, it is not well understood yet what is the precise role of mitotic bookmarking on mitotic transcription as well as on the transcription reactivation waves. Ultimately, the core gene regulatory network driving the precise transcription reactivation dynamics remains to be identified. To address these questions, we developed a mathematical model to correct for the progressive desynchronization of cells and estimate gene expression dynamics with respect to a cell-cycle pseudotime. Furthermore, we used a multiple linear regression model to infer transcription factor activity dynamics. Our analysis allows us to characterize waves of transcription factor activities exiting mitosis and predict a core gene regulatory network responsible of the transcription reactivation dynamics. Moreover, we identified more than 60 transcription factors that are highly active during mitosis and represent new candidates of mitotic bookmarking factors which could be relevant therapeutic targets to control cell proliferation.

scholarly journals The transcription factor Zic4 acts as a transdifferentiation switch

2021 ◽  
Author(s):  
Matthias Christian Vogg ◽  
Jaroslav Ferenc ◽  
Wanda Christa Buzgariu ◽  
Chrystelle Perruchoud ◽  
Panagiotis Papasaikas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Gene Regulatory Network ◽  
Cell Fate ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Model System ◽  
Cell Identity ◽  
Transcriptional Switch ◽  
Gene Regulatory

The molecular mechanisms that maintain cell identities and prevent transdifferentiation remain mysterious. Interestingly, both dedifferentiation and transdifferentiation are transiently reshuffled during regeneration. Therefore, organisms that regenerate readily offer a fruitful paradigm to investigate the regulation of cell fate stability. Here, we used Hydra as a model system and show that Zic4 silencing is sufficient to induce transdifferentiation of tentacle into foot cells. We identified a Wnt-controlled Gene Regulatory Network that controls a transcriptional switch of cell identity. Furthermore, we show that this switch also controls the re-entry into the cell cycle. Our data indicate that maintenance of cell fate by a Wnt-controlled GRN is a key mechanism during both homeostasis and regeneration.

scholarly journals Characterisation of interactions between the pluripotency transcription factors Nanog, Oct4 and Sox2

2020 ◽  
Author(s):  
Tapan Kumar Mistri ◽  
David Kelly ◽  
John Mak ◽  
Douglas Colby ◽  
Nicholas Mullin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Network ◽  
Single Molecule ◽  
Regulatory Network ◽  
Es Cells ◽  
Control Cell ◽  
Embryonic Stem ◽  
Correlation Spectroscopy ◽  
Dependent Manner ◽  
Gene Regulatory

ABSTRACTThe pluripotency transcription factors (TFs) Nanog, Sox2, and Oct4 are at the centre of the gene regulatory network that controls cell identity in embryonic stem (ES) cells. However, the mechanisms by which these factors control cell fate, and their interactions with one another are not fully understood. Here we combine biophysical and novel biochemical assays to assess how these factors interact with each other quantitatively. A new confocal microscopy method to detect binding of a target protein to a fluorescently labelled partner (coimmunoprecipitation bead imaging microscopy [CBIM]) is presented and used to demonstrate homotypic binding of Nanog and heterotypic binding between Nanog and Sox2 and between Nanog and Oct4. Using fluorescence correlation spectroscopy we show that in solution, Nanog but not Oct4 or Sox2 can form homodimers. Fluorescence Cross Correlation Spectroscopy shows that the affinity of Nanog for dimer formation is in the order Sox2 > Nanog > Oct4. Importantly, live cell analysis demonstrate the existence of Nanog homodimers in vivo. While Sox2 and Oct4 bind one another in a DNA-dependent manner, Nanog appears not to bridge Sox2 and Oct4, even though Nanog binds both Sox2 and Oct4 individually. Together these findings extend understanding of the molecular interactions occurring between these central mediators of the pluripotency gene regulatory network at the single molecule level.

scholarly journals Odd-paired controls frequency doubling in Drosophila segmentation by altering the pair-rule gene regulatory network

2016 ◽  
Author(s):  
Erik Clark ◽  
Michael Akam
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Frequency Doubling ◽  
Anteroposterior Patterning ◽  
Regulatory Interactions ◽  
Pair Rule Gene ◽  
Gene Regulatory ◽  
Pair Rule

ABSTRACTThe Drosophila embryo transiently exhibits a double segment periodicity, defined by the expression of seven “pair-rule” genes, each in a pattern of seven stripes. At gastrulation, interactions between the pair-rule genes lead to frequency doubling and the patterning of fourteen parasegment boundaries. In contrast to earlier stages of Drosophila anteroposterior patterning, this transition is not well understood. By carefully analysing the spatiotemporal dynamics of pair-rule gene expression, we demonstrate that frequency-doubling is precipitated by multiple coordinated changes to the network of regulatory interactions between the pair-rule genes. We identify the broadly expressed but temporally patterned transcription factor, Odd-paired (Opa/Zic), as the cause of these changes, and show that the patterning of the even-numbered parasegment boundaries relies on Opa-dependent regulatory interactions. Our findings indicate that the pair-rule gene regulatory network has a temporally-modulated topology, permitting the pair-rule genes to play stage-specific patterning roles.

scholarly journals Segmentation and patterning of the vertebrate hindbrain

Development ◽  
2021 ◽  
Vol 148 (15) ◽  
Author(s):  
Robb Krumlauf ◽  
David G. Wilkinson
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Dynamic Regulation ◽  
Regulatory Cascade ◽  
Gene Regulatory ◽  
Key Aspects ◽  
Cell Segregation ◽  
A Site

ABSTRACT During early development, the hindbrain is sub-divided into rhombomeres that underlie the organisation of neurons and adjacent craniofacial tissues. A gene regulatory network of signals and transcription factors establish and pattern segments with a distinct anteroposterior identity. Initially, the borders of segmental gene expression are imprecise, but then become sharply defined, and specialised boundary cells form. In this Review, we summarise key aspects of the conserved regulatory cascade that underlies the formation of hindbrain segments. We describe how the pattern is sharpened and stabilised through the dynamic regulation of cell identity, acting in parallel with cell segregation. Finally, we discuss evidence that boundary cells have roles in local patterning, and act as a site of neurogenesis within the hindbrain.

scholarly journals Integrated Epigenetic Mapping of Human and Mouse Salivary Gene Regulation

2018 ◽  
Vol 98 (2) ◽  
pp. 209-217 ◽  
Author(s):  
D.G. Michael ◽  
T.J.F. Pranzatelli ◽  
B.M. Warner ◽  
H. Yin ◽  
J.A. Chiorini
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Salivary Gland ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Factors Associated ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Cis And Trans ◽  
Genomic Footprinting

Significant effort has been applied to identify the genome-wide gene expression profiles associated with salivary gland development and pathophysiology. However, relatively little is known about the regulators that control salivary gland gene expression. We integrated data from DNase1 digital genomic footprinting, RNA-seq, and gene expression microarrays to comprehensively characterize the cis- and trans-regulatory components controlling gene expression of the healthy submandibular salivary gland. Analysis of 32 human tissues and 87 mouse tissues was performed to identify the highly expressed and tissue-enriched transcription factors driving salivary gland gene expression. Following RNA analysis, protein expression levels and subcellular localization of 39 salivary transcription factors were confirmed by immunohistochemistry. These expression analyses revealed that the salivary gland highly expresses transcription factors associated with endoplasmic reticulum stress, human T-cell lymphotrophic virus 1 expression, and Epstein-Barr virus reactivation. DNase1 digital genomic footprinting to a depth of 333,426,353 reads was performed and utilized to generate a salivary gland gene regulatory network describing the genome-wide chromatin accessibility and transcription factor binding of the salivary gland at a single-nucleotide resolution. Analysis of the DNase1 gene regulatory network identified dense interconnectivity among PLAG1, MYB, and 13 other transcription factors associated with balanced chromosomal translocations and salivary gland tumors. Collectively, these analyses provide a comprehensive atlas of the cis- and trans-regulators of the salivary gland and highlight known aberrantly regulated pathways of diseases affecting the salivary glands.

scholarly journals Study on the Relationship between the miRNA-centered ceRNA Regulatory Network and Fatigue

2021 ◽  
Author(s):  
Xingzhe Yang ◽  
Feng Li ◽  
Jie Ma ◽  
Yan Liu ◽  
Xuejiao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Hot Spot ◽  
Genetic Research ◽  
Noncoding Rnas ◽  
Messenger Rnas ◽  
Effective Prevention ◽  
Gene Regulatory ◽  
The Relationship

AbstractIn recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.

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