Analysis of NFATc1-Centered Transcription Factor Regulatory Networks in Osteoclast Formation

Author(s):  
Masahiro Shinohara ◽  
Hiroshi Takayanagi
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Albert T. Young ◽  
Xavier Carette ◽  
Michaela Helmel ◽  
Hanno Steen ◽  
Robert N. Husson ◽  
...  

AbstractThe ability of Mycobacterium tuberculosis (Mtb) to adapt to diverse stresses in its host environment is crucial for pathogenesis. Two essential Mtb serine/threonine protein kinases, PknA and PknB, regulate cell growth in response to environmental stimuli, but little is known about their downstream effects. By combining RNA-Seq data, following treatment with either an inhibitor of both PknA and PknB or an inactive control, with publicly available ChIP-Seq and protein–protein interaction data for transcription factors, we show that the Mtb transcription factor (TF) regulatory network propagates the effects of kinase inhibition and leads to widespread changes in regulatory programs involved in cell wall integrity, stress response, and energy production, among others. We also observe that changes in TF regulatory activity correlate with kinase-specific phosphorylation of those TFs. In addition to characterizing the downstream regulatory effects of PknA/PknB inhibition, this demonstrates the need for regulatory network approaches that can incorporate signal-driven transcription factor modifications.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah E. Pierce ◽  
Jeffrey M. Granja ◽  
William J. Greenleaf

AbstractChromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yongsheng Li ◽  
Tingting Shao ◽  
Chunjie Jiang ◽  
Jing Bai ◽  
Zishan Wang ◽  
...  

2014 ◽  
Vol 31 (10) ◽  
pp. 2672-2688 ◽  
Author(s):  
Alys M. Cheatle Jarvela ◽  
Lisa Brubaker ◽  
Anastasia Vedenko ◽  
Anisha Gupta ◽  
Bruce A. Armitage ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush

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.


2008 ◽  
Vol 4 (4) ◽  
pp. 309 ◽  
Author(s):  
Christian A. Grove ◽  
Albertha J. M. Walhout

Plants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 201 ◽  
Author(s):  
María José López-Galiano ◽  
Inmaculada García-Robles ◽  
Ana I. González-Hernández ◽  
Gemma Camañes ◽  
Begonya Vicedo ◽  
...  

In a scenario of global climate change, water scarcity is a major threat for agriculture, severely limiting crop yields. Therefore, alternatives are urgently needed for improving plant adaptation to drought stress. Among them, gene expression reprogramming by microRNAs (miRNAs) might offer a biotechnologically sound strategy. Drought-responsive miRNAs have been reported in many plant species, and some of them are known to participate in complex regulatory networks via their regulation of transcription factors involved in water stress signaling. We explored the role of miR159 in the response of Solanum lycopersicum Mill. plants to drought stress by analyzing the expression of sly-miR159 and its target SlMYB transcription factor genes in tomato plants of cv. Ailsa Craig grown in deprived water conditions or in response to mechanical damage caused by the Colorado potato beetle, a devastating insect pest of Solanaceae plants. Results showed that sly-miR159 regulatory function in the tomato plants response to distinct stresses might be mediated by differential stress-specific MYB transcription factor targeting. sly-miR159 targeting of SlMYB33 transcription factor transcript correlated with accumulation of the osmoprotective compounds proline and putrescine, which promote drought tolerance. This highlights the potential role of sly-miR159 in tomato plants’ adaptation to water deficit conditions.


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