scholarly journals Novel PAX6 Binding Sites in the Human Genome and the Role of Repetitive Elements in the Evolution of Gene Regulation

2002 ◽  
Vol 12 (11) ◽  
pp. 1716-1722 ◽  
Author(s):  
Y.-H. Zhou
Keyword(s):  
Gene Regulation ◽  
Human Genome ◽  
Binding Sites ◽  
Repetitive Elements ◽  
Evolution Of Gene Regulation

scholarly journals Functional disease architectures reveal unique biological role of transposable elements

2018 ◽  
Author(s):  
Farhad Hormozdiari ◽  
Bryce van de Geijn ◽  
Joseph Nasser ◽  
Omer Weissbrod ◽  
Steven Gazal ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transposable Elements ◽  
Human Genome ◽  
Complex Traits ◽  
Genetic Architecture ◽  
Biological Function ◽  
Functional Annotations ◽  
Evolution Of Gene Regulation ◽  
Analyze Data

AbstractTransposable elements (TE) comprise roughly half of the human genome. Though initially derided as “junk DNA”, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases and complex traits remains unknown. Here, we analyze data from 41 independent diseases and complex traits (average N=320K) to draw three main conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39±2% of heritability; enrichment of 0.72±0.03; 0.38-1.23 enrichment across four main TE classes), TE explain substantially more heritability than expected based on their depletion for known functional annotations (expected enrichment of 0.35±0.03; 2.11x ratio of true vs. expected enrichment). This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function; SNPs inside the oldest 20% of TE explain 2.45x more heritability than SNPs inside the youngest 20% of TE. Third, Short Interspersed Nuclear Elements (SINE; one of the four main TE classes) are far more enriched for blood traits (2.05±0.30) than for other traits (0.96±0.09); this difference is far greater than expected based on the weaker depletion of SINEs for regulatory annotations in blood compared to other tissues. Our results elucidate the biological roles that TE play in the genetic architecture of diseases and complex traits.

CTCF, cohesin, and histone variants: connecting the genome

2011 ◽  
Vol 89 (5) ◽  
pp. 505-513 ◽  
Author(s):  
Jean-François Millau ◽  
Luc Gaudreau
Keyword(s):  
Human Genome ◽  
Binding Sites ◽  
Genome Organization ◽  
Histone Variants ◽  
Ctcf Binding ◽  
Recent Advances ◽  
Genome Wide ◽  
Gene Regulations

During the last decades our view of the genome organization has changed. We moved from a linear view to a looped view of the genome. It is now well established that inter- and intra-connections occur between chromosomes and play a major role in gene regulations. These interconnections are mainly orchestrated by the CTCF protein, which is also known as the “master weaver” of the genome. Recent advances in sequencing and genome-wide studies revealed that CTCF binds to DNA at thousands of sites within the human genome, providing the possibility to form thousands of genomic connection hubs. Strikingly, two histone variants, namely H2A.Z and H3.3, strongly co-localize at CTCF binding sites. In this article, we will review the recent advances in CTCF biology and discuss the role of histone variants H2A.Z and H3.3 at CTCF binding sites.

scholarly journals The Role of Nucleosome Positioning in the Evolution of Gene Regulation

PLoS Biology ◽  
2010 ◽  
Vol 8 (7) ◽  
pp. e1000414 ◽  
Author(s):  
Alexander M. Tsankov ◽  
Dawn Anne Thompson ◽  
Amanda Socha ◽  
Aviv Regev ◽  
Oliver J. Rando
Keyword(s):  
Gene Regulation ◽  
Nucleosome Positioning ◽  
Evolution Of Gene Regulation

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

Non-pharmacological Strategies Against Systemic Inflammation: Molecular Basis and Clinical Evidence

2020 ◽  
Vol 26 (22) ◽  
pp. 2620-2629 ◽  
Author(s):  
Rita Del Pinto ◽  
Davide Pietropaoli ◽  
Annalisa Monaco ◽  
Giovambattista Desideri ◽  
Claudio Ferri ◽  
...  
Keyword(s):  
Human Genome ◽  
Systemic Inflammation ◽  
Clinical Evidence ◽  
Metabolic Diseases ◽  
Lifestyle Changes ◽  
Common Denominator ◽  
Active Lifestyle ◽  
Systemic Impact ◽  
Public Health Strategies

Systemic inflammation is a common denominator to a variety of cardiovascular (CV) and non-CV diseases and relative risk factors, including hypertension and its control, metabolic diseases, rheumatic disorders, and those affecting the gastrointestinal tract. Besides medications, a non-pharmacological approach encompassing lifestyle changes and other complementary measures is mentioned in several updated guidelines on the management of these conditions. We performed an updated narrative review on the mechanisms behind the systemic impact of inflammation and the role of non-pharmacological, complementary measures centered on lowering systemic phlogosis for preserving or restoring a good global health. The central role of genetics in shaping the immune response is discussed in conjunction with that of the microbiome, highlighting the interdependence and mutual influences between the human genome and microbial integrity, diversity, and functions. Several plausible strategies to modulate inflammation and restore balanced crosstalk between the human genome and the microbiome are then recapitulated, including dietary measures, active lifestyle, and other potential approaches to manipulate the resident microbial community. To date, evidence from high-quality human studies is sparse to allow the unconditioned inclusion of understudied, though plausible solutions against inflammation into public health strategies for global wellness. This gap claims further focused, well-designed research targeted at unravelling the mechanisms behind future personalized medicine.

Sign in / Sign up

Export Citation Format

Share Document