scholarly journals The nuclear receptor HNF4 drives a brush border gene program conserved across murine intestine, kidney, and embryonic yolk sac

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Chen ◽  
Shirley Luo ◽  
Abigail Dupre ◽  
Roshan P. Vasoya ◽  
Aditya Parthasarathy ◽  
...  
Keyword(s):  
Brush Border ◽  
Regulatory Networks ◽  
Critical Role ◽  
Yolk Sac ◽  
Apical Surface ◽  
Transcriptional Regulatory Networks ◽  
Chromatin Looping ◽  
Multiple Organs ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms

AbstractThe brush border is comprised of microvilli surface protrusions on the apical surface of epithelia. This specialized structure greatly increases absorptive surface area and plays crucial roles in human health. However, transcriptional regulatory networks controlling brush border genes are not fully understood. Here, we identify that hepatocyte nuclear factor 4 (HNF4) transcription factor is a conserved and important regulator of brush border gene program in multiple organs, such as intestine, kidney and yolk sac. Compromised brush border gene signatures and impaired transport were observed in these tissues upon HNF4 loss. By ChIP-seq, we find HNF4 binds and activates brush border genes in the intestine and kidney. H3K4me3 HiChIP-seq identifies that HNF4 loss results in impaired chromatin looping between enhancers and promoters at gene loci of brush border genes, and instead enhanced chromatin looping at gene loci of stress fiber genes in the intestine. This study provides comprehensive transcriptional regulatory mechanisms and a functional demonstration of a critical role for HNF4 in brush border gene regulation across multiple murine epithelial tissues.

scholarly journals Identification of COVID-19-relevant transcriptional regulatory networks and associated kinases as potential therapeutic targets

2020 ◽  
Author(s):  
Chen Su ◽  
Simon Rousseau ◽  
Amin Emad
Keyword(s):  
Epithelial Cells ◽  
Regulatory Networks ◽  
Therapeutic Targets ◽  
Airway Epithelial Cells ◽  
Regulatory Mechanisms ◽  
Interferon Response ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms ◽  
The Impact

ABSTRACTIdentification of transcriptional regulatory mechanisms and signaling networks involved in the response of host to infection by SARS-CoV-2 is a powerful approach that provides a systems biology view of gene expression programs involved in COVID-19 and may enable identification of novel therapeutic targets and strategies to mitigate the impact of this disease. In this study, we combined a series of recently developed computational tools to identify transcriptional regulatory networks involved in the response of epithelial cells to infection by SARS-CoV-2, and particularly regulatory mechanisms that are specific to this virus. In addition, using network-guided analyses, we identified signaling pathways that are associated with these networks and kinases that may regulate them. The results identified classical antiviral response pathways including Interferon response factors (IRFs), interferons (IFNs), and JAK-STAT signaling as key elements upregulated by SARS-CoV-2 in comparison to mock-treated cells. In addition, comparing SARS-Cov-2 infection of airway epithelial cells to other respiratory viruses identified pathways associated with regulation of inflammation (MAPK14) and immunity (BTK, MBX) that may contribute to exacerbate organ damage linked with complications of COVID-19. The regulatory networks identified herein reflect a combination of experimentally validated hits and novel pathways supporting the computational pipeline to quickly narrow down promising avenue of investigations when facing an emerging and novel disease such as COVID-19.

Transcriptional Control of Parturition: Insights from Gene Regulation Studies in the Myometrium

2021 ◽  
Author(s):  
Nawrah Khader ◽  
Virlana M Shchuka ◽  
Oksana Shynlova ◽  
Jennifer A Mitchell
Keyword(s):  
Transcription Factors ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Progesterone Receptors ◽  
Activator Protein 1 ◽  
Transcriptional Regulatory Networks ◽  
Regulatory Pathways ◽  
Transcriptional Regulatory ◽  
Mechanistic Basis ◽  
Labour Onset

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.

scholarly journals Transcriptional Regulatory Networks Associate with Early Stages of Potato Virus X Infection of Solanum tuberosum

2021 ◽  
Vol 22 (6) ◽  
pp. 2837
Author(s):  
Venura Herath ◽  
Jeanmarie Verchot
Keyword(s):  
Potato Virus ◽  
Regulatory Networks ◽  
Potato Virus X ◽  
Early Response ◽  
Pathogen Resistance ◽  
Transcriptional Regulatory Networks ◽  
Unfolded Protein ◽  
Molecular Pattern ◽  
Transcriptional Regulatory ◽  
Protein Response

Potato virus X (PVX) belongs to genus Potexvirus. This study characterizes the cellular transcriptome responses to PVX infection in Russet potato at 2 and 3 days post infection (dpi). Among the 1242 differentially expressed genes (DEGs), 268 genes were upregulated, and 37 genes were downregulated at 2 dpi while 677 genes were upregulated, and 265 genes were downregulated at 3 dpi. DEGs related to signal transduction, stress response, and redox processes. Key stress related transcription factors were identified. Twenty-five pathogen resistance gene analogs linked to effector triggered immunity or pathogen-associated molecular pattern (PAMP)-triggered immunity were identified. Comparative analysis with Arabidopsis unfolded protein response (UPR) induced DEGs revealed genes associated with UPR and plasmodesmata transport that are likely needed to establish infection. In conclusion, this study provides an insight on major transcriptional regulatory networked involved in early response to PVX infection and establishment.

scholarly journals Genetics and Epigenetics of Atrial Fibrillation

2020 ◽  
Vol 21 (16) ◽  
pp. 5717 ◽  
Author(s):  
Estefanía Lozano-Velasco ◽  
Diego Franco ◽  
Amelia Aranega ◽  
Houria Daimi
Keyword(s):  
Atrial Fibrillation ◽  
Regulatory Networks ◽  
Association Studies ◽  
Functional Characterization ◽  
The Elderly ◽  
Supraventricular Arrhythmia ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms

Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence exponentially increases with age and could reach up to 8% in the elderly population. The management of AF is a complex issue that is addressed by extensive ongoing basic and clinical research. AF centers around different types of disturbances, including ion channel dysfunction, Ca2+-handling abnormalities, and structural remodeling. Genome-wide association studies (GWAS) have uncovered over 100 genetic loci associated with AF. Most of these loci point to ion channels, distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Recently, the discovery of post-transcriptional regulatory mechanisms, involving non-coding RNAs (especially microRNAs), DNA methylation, and histone modification, has allowed to decipher how a normal heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. This review aims to provide a current state of the field regarding the identification and functional characterization of AF-related epigenetic regulatory networks

scholarly journals Flynet: a genomic resource for Drosophila melanogaster transcriptional regulatory networks

2009 ◽  
Vol 25 (22) ◽  
pp. 3001-3004 ◽  
Author(s):  
F. Tian ◽  
P. K. Shah ◽  
X. Liu ◽  
N. Negre ◽  
J. Chen ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Genomic Resource

Transcriptional regulatory networks evoked by both flow and pharmacophores that confer endothelial atheroprotection

2006 ◽  
Vol 45 (3) ◽  
pp. e47
Author(s):  
Kush M. Parmar ◽  
H. Benjamin Larman ◽  
Vinod Nambudiri ◽  
Guohao Dai ◽  
Yuzhi Zhang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory
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