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 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 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 Identification of Regulatory DNA Elements Using Genome-wide Mapping of DNase I Hypersensitive Sites during Tomato Fruit Development

2016 ◽  
Vol 9 (8) ◽  
pp. 1168-1182 ◽  
Author(s):  
Zhengkun Qiu ◽  
Ren Li ◽  
Shuaibin Zhang ◽  
Ketao Wang ◽  
Meng Xu ◽  
...  
Keyword(s):  
Fruit Development ◽  
Tomato Fruit ◽  
Dnase I ◽  
Dnase I Hypersensitive Sites ◽  
Genome Wide ◽  
Hypersensitive Sites ◽  
Dna Elements ◽  
Regulatory Dna

The prediction of human DNase I hypersensitive sites based on DNA sequence information

2021 ◽  
Vol 209 ◽  
pp. 104223
Author(s):  
Wei Su ◽  
Fang Wang ◽  
Jiu-Xin Tan ◽  
Fu-Ying Dao ◽  
Hui Yang ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Dnase I ◽  
Sequence Information ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites

The chromatin structure of Saccharomyces cerevisiae autonomously replicating sequences changes during the cell division cycle

1991 ◽  
Vol 11 (10) ◽  
pp. 5301-5311
Author(s):  
J A Brown ◽  
S G Holmes ◽  
M M Smith
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Division ◽  
Chromatin Structure ◽  
Dnase I ◽  
S Phase ◽  
Cell Division Cycle ◽  
Characteristic Change ◽  
The Core ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites

The chromatin structures of two well-characterized autonomously replicating sequence (ARS) elements were examined at their chromosomal sites during the cell division cycle in Saccharomyces cerevisiae. The H4 ARS is located near one of the duplicate nonallelic histone H4 genes, while ARS1 is present near the TRP1 gene. Cells blocked in G1 either by alpha-factor arrest or by nitrogen starvation had two DNase I-hypersensitive sites of about equal intensity in the ARS element. This pattern of DNase I-hypersensitive sites was altered in synchronous cultures allowed to proceed into S phase. In addition to a general increase in DNase I sensitivity around the core consensus sequence, the DNase I-hypersensitive site closest to the core consensus became more nuclease sensitive than the distal site. This change in chromatin structure was restricted to the ARS region and depended on replication since cdc7 cells blocked near the time of replication initiation did not undergo the transition. Subsequent release of arrested cdc7 cells restored entry into S phase and was accompanied by the characteristic change in ARS chromatin structure.

scholarly journals Histone H3K4me1 strongly activates the DNase I hypersensitive sites in super-enhancers than those in typical enhancers

2021 ◽  
Author(s):  
Yujin Kang ◽  
Jin Kang ◽  
AeRi Kim
Keyword(s):  
Target Genes ◽  
K562 Cells ◽  
Dnase I ◽  
Histone Methyltransferases ◽  
Dnase I Hypersensitive Sites ◽  
Catalytic Domains ◽  
Enhancer Rna ◽  
Super Enhancer ◽  
Hypersensitive Sites ◽  
Histone H3k27

Super-enhancers, which consist of multiple enhancer elements, are occupied by master transcription factors and coactivators, such as Mediator, and are highly acetylated at histone H3K27. Here, we have characterized the super-enhancers in terms of DNase I hypersensitive sites (DHSs) by analyzing publicly available ChIP-seq and DNase-seq data of K562 cells and compared to the DHSs in typical enhancers. DHSs in the super-enhancers were highly marked by histone H3K4me1 than DHSs in typical enhancers. Loss of H3K4me1 by the deletion of catalytic domains in histone methyltransferases MLL3 and MLL4 remarkably decreased histone H3K27ac and histone H3 depletion at super-enhancer DHSs than at typical enhancer DHSs. The levels of enhancer RNA (eRNA) transcripts and mRNA transcripts from the putative target genes were notably reduced at and near super-enhancer DHSs than typical enhancer DHSs following H3K4me1 loss. These results indicate that histone H3K4me1 is a marker for DHSs in super-enhancers and that this modification has a more significant impact on the activation of super-enhancer DHSs than typical enhancer DHSs.

Correlation between patterns of DNase I-hypersensitive sites and upstream promoter activity of the human epsilon-globin gene at different stages of erythroid development

1990 ◽  
Vol 10 (3) ◽  
pp. 1199-1208
Author(s):  
P Bushel ◽  
K Rego ◽  
L Mendelsohn ◽  
M Allan
Keyword(s):  
Globin Gene ◽  
K562 Cells ◽  
Dnase I ◽  
Base Pairs ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
Hel Cells ◽  
Globin Synthesis ◽  
Erythroleukemic Cell ◽  
Erythroid Development

DNA 5' to the human epsilon-globin gene exhibits unique patterns of DNase I-hypersensitive sites (DHS) in three human erythroleukemic cell lines which represent the embryonic (K562), fetal (HEL), and adult (KMOE) stages of erythroid development. We have mapped 10 epsilon-globin DHS in K562 cells, in which the epsilon-globin gene is maximally active. Major sites are located -11.7, -10.5, -6.5, -2.2 kilobase pairs (kbp) and -200 base pairs (bp) upstream of the gene and directly over the major cap site. Minor sites are located -5.5, -4.5, and -1.48 kbp and -900 bp upstream of the cap site. In HEL cells, in which the epsilon-globin gene is expressed at extremely low levels, the -11.7-, -10.5-, -5.5-, -4.5-, and -2.2-kbp DHS are no longer detectable; the -200-bp site is approximately 300-fold less sensitive to DNase I; and the -1.48-kbp, -900-bp, and major cap site DHS are 3- to 4-fold less sensitive. Only the DHS located -6.5 kbp relative to the major cap site is detectable at all three stages of erythroid development, including KMOE cells in which epsilon-globin synthesis is undetectable. We suggest that this site may be implicated in maintaining the entire beta-globin cluster in an active chromatin conformation. The five DHS downstream of the -6.5-kbp element possess associated promoters. Thus two distinct types of DHS exist--promoter positive and promoter negative. In HEL cells, all the upstream promoters are inactivated, although the -1.48-kbp and -900- and -200-bp DHS are still present. This suggests that the maintenance of DHS and regulation of their associated promoters occur by independent mechanisms. The inactivation of the upstream promoters in HEL cells while the major cap site remains active represents a unique pattern of expression and suggests that HEL cells possess regulatory factors which specifically down regulate the epsilon-globin upstream promoters.

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