scholarly journals Insights into Gene Regulatory Networks in Chondrocytes

2019 ◽  
Vol 20 (24) ◽  
pp. 6324 ◽  
Author(s):  
Hironori Hojo ◽  
Shinsuke Ohba
Keyword(s):  
Transcription Factors ◽  
Dna Sequences ◽  
Regulatory Networks ◽  
Developmental Process ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Gene Expressions ◽  
A Genome ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Chondrogenesis is a key developmental process that molds the framework of our body and generates the skeletal tissues by coupling with osteogenesis. The developmental processes are well-coordinated by spatiotemporal gene expressions, which are hardwired with gene regulatory elements. Those elements exist as thousands of modules of DNA sequences on the genome. Transcription factors function as key regulatory proteins by binding to regulatory elements and recruiting cofactors. Over the past 30 years, extensive attempts have been made to identify gene regulatory mechanisms in chondrogenesis, mainly through biochemical approaches and genetics. More recently, newly developed next-generation sequencers (NGS) have identified thousands of gene regulatory elements on a genome scale, and provided novel insights into the multiple layers of gene regulatory mechanisms, including the modes of actions of transcription factors, post-translational histone modifications, chromatin accessibility, the concept of pioneer factors, and three-dimensional chromatin architecture. In this review, we summarize the studies that have improved our understanding of the gene regulatory mechanisms in chondrogenesis, from the historical studies to the more recent works using NGS. Finally, we consider the future perspectives, including efforts to improve our understanding of the gene regulatory landscape in chondrogenesis and potential applications to the treatment of chondrocyte-related diseases.

scholarly journals ENDOGENOUS RETROVIRUSES AS GENETIC MODULES THAT SHAPE THE GENOME REGULATORY NETWORKS DURING EVOLUTION

2018 ◽  
Keyword(s):  
Regulatory Networks ◽  
Gene Activation ◽  
Cell Types ◽  
Regulatory Elements ◽  
Endogenous Retroviruses ◽  
Protein Coding ◽  
Transcriptional Enhancers ◽  
Wide Range ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Endogenous retroviruses (ERV) are the descendants of exogenous retroviruses that integrated into the germ cells genome, fixed and became inheritable. ERVs have evolved transcriptional enhancers and promoters that allow their replication in a wide range of tissue. Because ERVs comprise the regulatory elements it could be assume that ERVs capable to shape and reshape genomic regulatory networks by inserting their promoters and enhancers in new genomic loci upon retrotransposition. Thus retroransposition events can build new regulatory regions and lead to a new pattern of gene activation in the cell. In this review we summarize evidence which revealed that ERVs provide a plethora of novel gene regulatory elements, including tissue specific promoters and enhancers for protein-coding genes or long noncoding RNAs in a wide range of cell types. The accumulated findings support the hypothesis that the ERVs have rewired the gene regulatory networks and act as a major source of genomic regulatory innovation during evolution.

scholarly journals AP-1 Imprints a Reversible Transcriptional Program of Senescent Cells

2019 ◽  
Author(s):  
Ricardo Iván Martínez-Zamudio ◽  
Pierre-François Roux ◽  
José Américo N L F de Freitas ◽  
Lucas Robinson ◽  
Gregory Doré ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Regulatory Elements ◽  
Activator Protein 1 ◽  
Dynamic Nature ◽  
Dynamic Analyses ◽  
Gene Regulatory Elements ◽  
Sequential Activation ◽  
Gene Regulatory ◽  
Senescence Program ◽  
Organizational Principles

SUMMARYSenescent cells play important physiological- and pathophysiological roles in tumor suppression, tissue regeneration, and aging. While select genetic and epigenetic elements crucial for senescence induction were identified, the dynamics, underlying epigenetic mechanisms, and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding a deliberate therapeutic manipulation of these dynamic processes. Here, we show, using dynamic analyses of transcriptome and epigenome profiles, that the epigenetic state of enhancers predetermines their sequential activation during senescence. We demonstrate that activator protein 1 (AP-1) ‘imprints’ the senescence enhancer landscape effectively regulating transcriptional activities pertinent to the timely execution of the senescence program. We define and validate a hierarchical transcription factor (TF) network model and demonstrate its effectiveness for the design of senescence reprogramming experiments. Together, our findings define the dynamic nature and organizational principles of gene-regulatory elements driving the senescence program and reveal promising inroads for therapeutic manipulation of senescent cells.

scholarly journals Cell-specific chromatin landscape of human coronary artery resolves regulatory mechanisms of disease risk

2021 ◽  
Author(s):  
Adam W. Turner ◽  
Sheng'en Hu ◽  
Jose Verdezoto Mosquera ◽  
Wei Feng Ma ◽  
Chani Hodonsky ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Coronary Artery ◽  
Single Cell ◽  
Dna Sequences ◽  
Association Studies ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Genome Wide Association Studies ◽  
Risk Variants ◽  
Cad Risk

Coronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across several cell types. Genome-wide association studies (GWAS) have identified over 170 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis-regulatory elements (CREs). Here, we applied single-cell ATAC-seq to profile 28,316 cells across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters. We mapped ~320,000 accessible sites across all cells, identified cell type-specific elements, transcription factors, and prioritized functional CAD risk variants via quantitative trait locus and sequence-based predictive modeling. We identified a number of candidate mechanisms for smooth muscle cell transition states and identified putative binding sites for risk variants. We further employed DNA element to gene linkage to nominate disease-associated key driver transcription factors such as PRDM16 and TBX2. This single cell atlas provides a critical step towards interpreting cis-regulatory mechanisms in the vessel wall across the continuum of CAD risk.

scholarly journals Cell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christopher A. Brosnan ◽  
Alexander J. Palmer ◽  
Steven Zuryn
Keyword(s):  
Caenorhabditis Elegans ◽  
Regulatory Networks ◽  
Regulatory Mechanisms ◽  
Cell Type ◽  
A Genome ◽  
Temporal Flexibility ◽  
Small Regulatory Rnas ◽  
Cell Type Specific ◽  
Single Cell Type ◽  
Regulated Gene Expression

AbstractMulticellularity has coincided with the evolution of microRNAs (miRNAs), small regulatory RNAs that are integrated into cellular differentiation and homeostatic gene-regulatory networks. However, the regulatory mechanisms underpinning miRNA activity have remained largely obscured because of the precise, and thus difficult to access, cellular contexts under which they operate. To resolve these, we have generated a genome-wide map of active miRNAs in Caenorhabditis elegans by revealing cell-type-specific patterns of miRNAs loaded into Argonaute (AGO) silencing complexes. Epitope-labelled AGO proteins were selectively expressed and immunoprecipitated from three distinct tissue types and associated miRNAs sequenced. In addition to providing information on biological function, we define adaptable miRNA:AGO interactions with single-cell-type and AGO-specific resolution. We demonstrate spatial and temporal dynamicism, flexibility of miRNA loading, and suggest miRNA regulatory mechanisms via AGO selectivity in different tissues and during ageing. Additionally, we resolve widespread changes in AGO-regulated gene expression by analysing translatomes specifically in neurons.

scholarly journals Exploring functionally annotated transcriptional consensus regulatory elements with CONREL

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Davide Dalfovo ◽  
Samuel Valentini ◽  
Alessandro Romanel
Keyword(s):  
Cell Lines ◽  
Web Application ◽  
Regulatory Networks ◽  
Regulatory Elements ◽  
Levels Of Abstraction ◽  
Binding Motifs ◽  
Extensive Collection ◽  
Transcription Factor Binding Motifs ◽  
Gene Regulatory ◽  
Genomic Regions

Abstract Understanding the interaction between human genome regulatory elements and transcription factors is fundamental to elucidate the structure of gene regulatory networks. Here we present CONREL, a web application that allows for the exploration of functionally annotated transcriptional ‘consensus’ regulatory elements at different levels of abstraction. CONREL provides an extensive collection of consensus promoters, enhancers and active enhancers for 198 cell-lines across 38 tissue types, which are also combined to provide global consensuses. In addition, 1000 Genomes Project genotype data and the ‘total binding affinity’ of thousands of transcription factor binding motifs at genomic regulatory elements is fully combined and exploited to characterize and annotate functional properties of our collection. Comparison with other available resources highlights the strengths and advantages of CONREL. CONREL can be used to explore genomic loci, specific genes or genomic regions of interest across different cell lines and tissue types. The resource is freely available at https://bcglab.cibio.unitn.it/conrel.

scholarly journals Binding of an X-Specific Condensin Correlates with a Reduction in Active Histone Modifications at Gene Regulatory Elements

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 729-742 ◽  
Author(s):  
Lena Annika Street ◽  
Ana Karina Morao ◽  
Lara Heermans Winterkorn ◽  
Chen-Yu Jiao ◽  
Sarah Elizabeth Albritton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Chromatin Immunoprecipitation ◽  
Protein Complexes ◽  
Regulatory Elements ◽  
Evolutionarily Conserved ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Regulatory Sites

Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In Caenorhabditis elegans, a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses X chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using chromatin immunoprecipitation sequencing and mRNA sequencing. Across the X, the DCC accumulates at accessible gene regulatory sites in active chromatin and not heterochromatin. The DCC is required for reducing the levels of activating histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces gene expression, thus establishing a direct link between DCC binding and repression. Together, our results indicate that DCC-mediated transcription repression is associated with a reduction in the activity of X chromosomal gene regulatory elements.

scholarly journals Chicken beta B1-crystallin gene expression: presence of conserved functional polyomavirus enhancer-like and octamer binding-like promoter elements found in non-lens genes.

1991 ◽  
Vol 11 (3) ◽  
pp. 1488-1499 ◽  
Author(s):  
H J Roth ◽  
G C Das ◽  
J Piatigorsky
Keyword(s):  
Transcription Factors ◽  
Hela Cell ◽  
Dna Sequences ◽  
Nuclear Extract ◽  
Regulatory Elements ◽  
Dnase I ◽  
Flanking Sequence ◽  
Mobility Shift ◽  
Promoter Elements ◽  
Dnase I Footprinting

Expression of the chicken beta B1-crystallin gene was examined. Northern (RNA) blot and primer extension analyses showed that while abundant in the lens, the beta B1 mRNA is absent from the liver, brain, heart, skeletal muscle, and fibroblasts of the chicken embryo, suggesting lens specificity. Promoter fragments ranging from 434 to 126 bp of 5'-flanking sequence (plus 30 bp of exon 1) of the beta B1 gene fused to the bacterial chloramphenicol acetyltransferase gene functioned much more efficiently in transfected embryonic chicken lens epithelial cells than in transfected primary muscle fibroblasts or HeLa cells. Transient expression of recombinant plasmids in cultured lens cells, DNase I footprinting, in vitro transcription in a HeLa cell extract, and gel mobility shift assays were used to identify putative functional promoter elements of the beta B1-crystallin gene. Sequence analysis revealed a number of potential regulatory elements between positions -126 and -53 of the beta B1 promoter, including two Sp1 sites, two octamer binding sequence-like sites (OL-1 and OL-2), and two polyomavirus enhancer-like sites (PL-1 and PL-2). Deletion and site-specific mutation experiments established the functional importance of PL-1 (-116 to -102), PL-2 (-90 to -76), and OL-2 (-75 to -68). DNase I footprinting using a lens or a HeLa cell nuclear extract and gel mobility shifts using a lens nuclear extract indicated the presence of putative lens transcription factors binding to these DNA sequences. Competition experiments provided evidence that PL-1 and PL-2 recognize the same or very similar factors, while OL-2 recognizes a different factor. Our data suggest that the same or closely related transcription factors found in many tissues are used for expression of the chicken beta B1-crystallin gene in the lens.

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