scholarly journals Atlas and developmental dynamics of mouse DNase I hypersensitive sites

2020 ◽  
Author(s):  
Charles E. Breeze ◽  
John Lazar ◽  
Tim Mercer ◽  
Jessica Halow ◽  
Ida Washington ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Dnase I ◽  
Mammalian Development ◽  
Mouse Development ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
Nucleotide Resolution ◽  
Developmental Dynamics ◽  
Regulatory Dna ◽  
Early Mammalian Development

AbstractEarly mammalian development is orchestrated by genome-encoded regulatory elements populated by a changing complement of regulatory factors, creating a dynamic chromatin landscape. To define the spatiotemporal organization of regulatory DNA landscapes during mouse development and maturation, we generated nucleotide-resolution DNA accessibility maps from 15 tissues sampled at 9 intervals spanning post-conception day 9.5 through early adult, and integrated these with 41 adult-stage DNase-seq profiles to create a global atlas of mouse regulatory DNA. Collectively, we delineated >1.8 million DNase I hypersensitive sites (DHSs), with the vast majority displaying temporal and tissue-selective patterning. Here we show that tissue regulatory DNA compartments show sharp embryonic-to-fetal transitions characterized by wholesale turnover of DHSs and progressive domination by a diminishing number of transcription factors. We show further that aligning mouse and human fetal development on a regulatory axis exposes disease-associated variation enriched in early intervals lacking human samples. Our results provide an expansive new resource for decoding mammalian developmental regulatory programs.

scholarly journals The Ly-6E.1 (Sca-1) gene requires a 3' chromatin-dependent region for high-level gamma-interferon-induced hematopoietic cell expression

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2750-2761 ◽  
Author(s):  
A Sinclair ◽  
B Daly ◽  
E Dzierzak
Keyword(s):  
Consensus Sequence ◽  
Hematopoietic Cells ◽  
Regulatory Elements ◽  
Dnase I ◽  
Gamma Interferon ◽  
Hematopoietic Cell ◽  
Hematopoietic Stem ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
High Level

The Ly-6E.1/A.2 gene product recognized by the Sca-1 antibody has been found on murine hematopoietic stem cells and some hematopoietic precursors, T lymphocytes, and nonhematopoietic cell lineages, suggesting a complex array of gene regulatory elements. The ability to use the Ly6E.1/A.2 transcriptional regulatory elements to direct expression of heterologous genes will allow for the manipulation of these cells during development and in hematopoietic cell transplantations. To identify the elements necessary for high-level expression, we have made deletion constructs of Ly-6E.1 gene flanking regions containing DNase I hypersensitive sites, tested them for expression in hematopoietic cells, and have performed kinetic analyses to correlate the appearance of hypersensitive sites with gene transcription and protein expression. We show that a 3′ region containing two DNase I hypersensitive sites at +8.7 and +8.9 kb is required for high-level, gamma-interferon (gamma-IFN)-induced expression of the Ly-6E.1 gene and that a consensus sequence for a gamma-IFN-responsive element localizes to the +8.7 site. We also provide a description of allele- and cell-specific DNase I hypersensitive site patterns of the Ly-6E.1 and Ly-6A.2 genes. Taken together, these data indicate that while both 5′ and 3′ hypersensitive sites are rapidly induced with gamma-IFN, the 3′ most distal hypersensitive sites are involved in directing high levels of expression of Sca-1 in hematopoietic cells.

scholarly journals Prediction of DNase I Hypersensitive Sites by Using Pseudo Nucleotide Compositions

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Pengmian Feng ◽  
Ning Jiang ◽  
Nan Liu
Keyword(s):  
Cost Effective ◽  
Dnase I ◽  
Support Vector ◽  
Jackknife Test ◽  
Dnase I Hypersensitive Sites ◽  
Proposed Model ◽  
Hypersensitive Sites ◽  
Dna Elements ◽  
Genomic Regions ◽  
Regulatory Dna

DNase I hypersensitive sites (DHS) associated with a wide variety of regulatory DNA elements. Knowledge about the locations of DHS is helpful for deciphering the function of noncoding genomic regions. With the acceleration of genome sequences in the postgenomic age, it is highly desired to develop cost-effective computational methods to identify DHS. In the present work, a support vector machine based model was proposed to identify DHS by using the pseudo dinucleotide composition. In the jackknife test, the proposed model obtained an accuracy of 83%, which is competitive with that of the existing method. This result suggests that the proposed model may become a useful tool for DHS identifications.

scholarly journals Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene

2002 ◽  
Vol 269 (2) ◽  
pp. 553-559 ◽  
Author(s):  
Marios Phylactides ◽  
Rebecca Rowntree ◽  
Hugh Nuthall ◽  
David Ussery ◽  
Ann Wheeler ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Dnase I ◽  
Cftr Gene ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites

scholarly journals Identifying DNase I hypersensitive sites as driver distal regulatory elements in breast cancer

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Matteo D′Antonio ◽  
Donate Weghorn ◽  
Agnieszka D′Antonio-Chronowska ◽  
Florence Coulet ◽  
Katrina M. Olson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regulatory Elements ◽  
Dnase I ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
Distal Regulatory Elements

scholarly journals DHSpred: support-vector-machine-based human DNase I hypersensitive sites prediction using the optimal features selected by random forest

2017 ◽  
Author(s):  
Balachandran Manavalan ◽  
Tae Hwan Shin ◽  
Gwang Lee
Keyword(s):  
Support Vector Machine ◽  
Random Forest ◽  
Dna Sequences ◽  
Feature Selection Method ◽  
Regulatory Elements ◽  
Dnase I ◽  
Support Vector ◽  
Large Set ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites

AbstractDNase I hypersensitive sites (DHSs) are genomic regions that provide important information regarding the presence of transcriptional regulatory elements and the state of chromatin. Therefore, identifying DHSs in uncharacterized DNA sequences is crucial for understanding their biological functions and mechanisms. Although many experimental methods have been proposed to identify DHSs, they have proven to be expensive for genome-wide application. Therefore, it is necessary to develop computational methods for DHS prediction. In this study, we proposed a support vector machine (SVM)-based method for predicting DHSs, called DHSpred (DNase I Hypersensitive Site predictor in human DNA sequences), which was trained with 174 optimal features. The optimal combination of features was identified from a large set that included nucleotide composition and di- and trinucleotide physicochemical properties, using a random forest algorithm. DHSpred achieved a Matthews correlation coefficient and accuracy of 0.660 and 0.871, respectively, which were 3% higher than those of control SVM predictors trained with non-optimized features, indicating the efficiency of the feature selection method. Furthermore, the performance of DHSpred was superior to that of state-of-the-art predictors. An online prediction server has been developed to assist the scientific community, and is freely available at:http://www.thegleelab.org/DHSpred.html.

scholarly journals Index and biological spectrum of accessible DNA elements in the human genome

2019 ◽  
Author(s):  
Wouter Meuleman ◽  
Alexander Muratov ◽  
Eric Rynes ◽  
Jessica Halow ◽  
Kristen Lee ◽  
...  
Keyword(s):  
Coordinate System ◽  
Human Genome ◽  
High Precision ◽  
Dnase I ◽  
Global Perspective ◽  
Phenotypic Trait ◽  
Protein Coding ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
Regulatory Dna

AbstractDNase I hypersensitive sites (DHSs) are generic markers of regulatory DNA and harbor disease- and phenotypic trait-associated genetic variation. We established high-precision maps of DNase I hypersensitive sites from 733 human biosamples encompassing 439 cell and tissue types and states, and integrated these to precisely delineate and numerically index ~3.6 million DHSs encoded within the human genome, providing a common coordinate system for regulatory DNA. Here we show that the expansive scale of cell and tissue states sampled exposes an unprecedented degree of stereotyped actuation of large sets of elements, signaling the operation of distinct genome-scale regulatory programs. We show further that the complex actuation patterns of individual elements can be captured comprehensively by a simple regulatory vocabulary reflecting their dominant cellular manifestation. This vocabulary, in turn, enables comprehensive and quantitative regulatory annotation of both protein-coding genes and the vast array of well-defined but poorly-characterized non-coding RNA genes. Finally, we show that the combination of high-precision DHSs and regulatory vocabularies markedly concentrate disease- and trait-associated non-coding genetic signals both along the genome and across cellular compartments. Taken together, our results provide a common and extensible coordinate system and vocabulary for human regulatory DNA, and a new global perspective on the architecture of human gene regulation.

scholarly journals Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci

2019 ◽  
Vol 40 (3) ◽  
pp. 432-440
Author(s):  
Juncheng Dai ◽  
Zhihua Li ◽  
Christopher I Amos ◽  
Rayjean J Hung ◽  
Adonina Tardon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
Regulatory Elements ◽  
Dnase I ◽  
Pathway Enrichment Analysis ◽  
Eqtl Analysis ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
Lung Cancer Susceptibility

AbstractDNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case–control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10–1.24, P = 8.45 × 10−7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89–0.95, P = 1.02 × 10−6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What’s more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10−4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.

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