scholarly journals Interdependence between histone marks and steps in Pol II transcription

2021 ◽  
Author(s):  
Charles Danko ◽  
Zhong Wang ◽  
Alexandra Chivu ◽  
Lauren Choate ◽  
Edward Rice ◽  
...  
Keyword(s):  
Machine Learning ◽  
Histone Modifications ◽  
Dnase I ◽  
Open Chromatin ◽  
Learning Tools ◽  
Pol Ii ◽  
Histone Marks ◽  
Chromatin States ◽  
Hypersensitive Sites

Abstract The role of histone modifications in transcription remains incompletely understood. Here we used experimental perturbations combined with sensitive machine learning tools that infer the distribution of histone marks using maps of nascent transcription. Transcription predicted the variation in active histone marks and complex chromatin states, like bivalent promoters, down to single-nucleosome resolution and at an accuracy that rivaled the correspondence between independent ChIP-seq experiments. Blocking transcription rapidly removed two punctate marks, H3K4me3 and H3K27ac, from chromatin indicating that transcription is required for active histone modifications. Transcription was also required for maintenance of H3K27me3 consistent with a role for RNA in recruiting PRC2. A subset of DNase-I hypersensitive sites were refractory to prediction, precluding models where transcription initiates pervasively at any open chromatin. Our results, in combination with past literature, support a model in which active histone modifications serve a supportive, rather than a regulatory, role in transcription.

scholarly journals A Quantitative Analysis of the Impact on Chromatin Accessibility by Histone Modifications and Binding of Transcription Factors in DNase I Hypersensitive Sites

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Peng Cui ◽  
Jing Li ◽  
Bo Sun ◽  
Menghuan Zhang ◽  
Baofeng Lian ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Quantitative Analysis ◽  
Histone Modifications ◽  
Chromatin Accessibility ◽  
Dnase I ◽  
Open Chromatin ◽  
Dnase I Hypersensitive Sites ◽  
Biological Phenomena ◽  
Hypersensitive Sites ◽  
The Impact

It is known that chromatin features such as histone modifications and the binding of transcription factors exert a significant impact on the “openness” of chromatin. In this study, we present a quantitative analysis of the genome-wide relationship between chromatin features and chromatin accessibility in DNase I hypersensitive sites. We found that these features show distinct preference to localize in open chromatin. In order to elucidate the exact impact, we derived quantitative models to directly predict the “openness” of chromatin using histone modification features and transcription factor binding features, respectively. We show that these two types of features are highly predictive for chromatin accessibility in a statistical viewpoint. Moreover, our results indicate that these features are highly redundant and only a small number of features are needed to achieve a very high predictive power. Our study provides new insights into the true biological phenomena and the combinatorial effects of chromatin features to differential DNase I hypersensitivity.

scholarly journals Chromatin Architecture near a Potential 3′ End of the Igh Locus Involves Modular Regulation of Histone Modifications during B-Cell Development and In Vivo Occupancy at CTCF Sites

2005 ◽  
Vol 25 (4) ◽  
pp. 1511-1525 ◽  
Author(s):  
Francine E. Garrett ◽  
Alexander V. Emelyanov ◽  
Manuel A. Sepulveda ◽  
Patrick Flanagan ◽  
Sabrina Volpi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Histone Modifications ◽  
Dnase I ◽  
B Cell Development ◽  
Open Chromatin ◽  
Developmentally Regulated ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites

ABSTRACT The murine Igh locus has a 3′ regulatory region (3′ RR) containing four enhancers (hs3A, hs1,2, hs3B, and hs4) at DNase I-hypersensitive sites. The 3′ RR exerts long-range effects on class switch recombination (CSR) to several isotypes through its control of germ line transcription. By measuring levels of acetylated histones H3 and H4 and of dimethylated H3 (K4) with chromatin immunoprecipitation assays, we found that early in B-cell development, chromatin encompassing the enhancers of the 3′ RR began to attain stepwise modifications typical of an open conformation. The hs4 enhancer was associated with active chromatin initially in pro- and pre-B cells and then together with hs3A, hs1,2, and hs3B in B and plasma cells. Histone modifications were similar in resting splenic B cells and in splenic B cells induced by lipopolysaccharide to undergo CSR. From the pro-B-cell stage onward, the ∼11-kb region immediately downstream of hs4 displayed H3 and H4 modifications indicative of open chromatin. This region contained newly identified DNase I-hypersensitive sites and several CTCF target sites, some of which were occupied in vivo in a developmentally regulated manner. The open chromatin environment of the extended 3′ RR in mature B cells was flanked by regions associated with dimethylated K9 of histone H3. Together, these data suggest that 3′ RR elements are located within a specific chromatin subdomain that contains CTCF binding sites and developmentally regulated modules.

scholarly journals Inferring time series chromatin states for promoter-enhancer pairs based on Hi-C data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Henriette Miko ◽  
Yunjiang Qiu ◽  
Bjoern Gaertner ◽  
Maike Sander ◽  
Uwe Ohler
Keyword(s):  
Time Series ◽  
Histone Modifications ◽  
Gene Activation ◽  
Expectation Maximization Algorithm ◽  
Chromatin State ◽  
Open Chromatin ◽  
Multiple Time ◽  
Enhancer Activity ◽  
Chromatin States ◽  
Multiple Time Points

Abstract Background Co-localized combinations of histone modifications (“chromatin states”) have been shown to correlate with promoter and enhancer activity. Changes in chromatin states over multiple time points (“chromatin state trajectories”) have previously been analyzed at promoter and enhancers separately. With the advent of time series Hi-C data it is now possible to connect promoters and enhancers and to analyze chromatin state trajectories at promoter-enhancer pairs. Results We present TimelessFlex, a framework for investigating chromatin state trajectories at promoters and enhancers and at promoter-enhancer pairs based on Hi-C information. TimelessFlex extends our previous approach Timeless, a Bayesian network for clustering multiple histone modification data sets at promoter and enhancer feature regions. We utilize time series ATAC-seq data measuring open chromatin to define promoters and enhancer candidates. We developed an expectation-maximization algorithm to assign promoters and enhancers to each other based on Hi-C interactions and jointly cluster their feature regions into paired chromatin state trajectories. We find jointly clustered promoter-enhancer pairs showing the same activation patterns on both sides but with a stronger trend at the enhancer side. While the promoter side remains accessible across the time series, the enhancer side becomes dynamically more open towards the gene activation time point. Promoter cluster patterns show strong correlations with gene expression signals, whereas Hi-C signals get only slightly stronger towards activation. The code of the framework is available at https://github.com/henriettemiko/TimelessFlex. Conclusions TimelessFlex clusters time series histone modifications at promoter-enhancer pairs based on Hi-C and it can identify distinct chromatin states at promoter and enhancer feature regions and their changes over time.

scholarly journals Synergistic and Additive Properties of the Beta-Globin Locus Control Region (LCR) Revealed by 5′HS3 Deletion Mutations: Implication for LCR Chromatin Architecture

2005 ◽  
Vol 25 (16) ◽  
pp. 7033-7041 ◽  
Author(s):  
Xiangdong Fang ◽  
Jin Sun ◽  
Ping Xiang ◽  
Man Yu ◽  
Patrick A. Navas ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Control Region ◽  
Chromatin Structure ◽  
Globin Gene ◽  
Dnase I ◽  
Beta Globin ◽  
Pol Ii ◽  
Dnase I Hypersensitive Sites ◽  
Chromatin Architecture ◽  
Hypersensitive Sites

ABSTRACT Deletion of the 234-bp core element of the DNase I hypersensitive site 3 (5′HS3) of the locus control region (LCR) in the context of a human beta-globin locus yeast artificial chromosome (β-YAC) results in profound effects on globin gene expression in transgenic mice. In contrast, deletion of a 2.3-kb 5′HS3 region, which includes the 234-bp core sequence, has a much milder phenotype. Here we report the effects of these deletions on chromatin structure in the beta-globin locus of adult erythroblasts. The 234-bp 5′HS3 deletion abolished histone acetylation throughout the β-globin locus; recruitment of RNA polymerase II (pol II) to the LCR and beta-globin gene promoter was reduced to a basal level; and formation of all the 5′ DNase I hypersensitive sites of the LCR was disrupted. The 2.3-kb 5′HS3 deletion mildly reduced the level of histone acetylation but did not change the profile across the whole locus; the 5′ DNase I hypersensitive sites of the LCR were formed, but to a lesser extent; and recruitment of pol II was reduced, but only marginally. These data support the hypothesis that the LCR forms a specific chromatin structure and acts as a single entity. Based on these results we elaborate on a model of LCR chromatin architecture which accommodates the distinct phenotypes of the 5′HS3 and HS3 core deletions.

Technology Applications in Managing Talents

2021 ◽  
pp. 157-170
Author(s):  
Pushpa Kataria
Keyword(s):  
Machine Learning ◽  
Learning Tools ◽  
New Era ◽  
Hiring Process ◽  
Hr Management ◽  
Transformative Development ◽  
Technology Applications ◽  
Talent Acquisition ◽  
Board Level

Human resource (HR) management is all about people; there is no doubt about it. However, in the contemporary era inbuilt by the technological revolution and transformative development, the tenets of HR are finding a new footing. Technology applications have changed facets of corporate houses from restructuring organizations to resources to manpower. It has been seen that HR technologies are playing a major role in managing talents in organizations. Artificial intelligence, robotic process automation, and machine learning add an edge to talent acquisition and management. Machine learning tools are primarily being used in acquiring talents and enabling the hiring process effectively and efficiently. Today, as every company is moving to a new era of digitalization and data management, managing and mapping talents pose a challenge to C-suite and board-level management. The present study highlights the role of technology in managing talents in a series of HR processes.

scholarly journals Sequential Histone Modifications at Hoxd4 Regulatory Regions Distinguish Anterior from Posterior Embryonic Compartments

2004 ◽  
Vol 24 (18) ◽  
pp. 8090-8103 ◽  
Author(s):  
Mojgan Rastegar ◽  
Laila Kobrossy ◽  
Erzsebet Nagy Kovacs ◽  
Isabel Rambaldi ◽  
Mark Featherstone
Keyword(s):  
Rna Polymerase Ii ◽  
Histone Modifications ◽  
Chromatin Immunoprecipitation ◽  
Gene Activation ◽  
Open Chromatin ◽  
Rna Pol Ii ◽  
Regulatory Regions ◽  
Pol Ii ◽  
Embryonic Tissues ◽  
Intervening Sequences

ABSTRACT Hox genes are differentially expressed along the embryonic anteroposterior axis. We used chromatin immunoprecipitation to detect chromatin changes at the Hoxd4 locus during neurogenesis in P19 cells and embryonic day 8.0 (E8.0) and E10.5 mouse embryos. During Hoxd4 induction in both systems, we observed that histone modifications typical of transcriptionally active chromatin occurred first at the 3′ neural enhancer and then at the promoter. Moreover, the sequential distribution of histone modifications between E8.0 and E10.5 was consistent with a spreading of open chromatin, starting with the enhancer, followed by successively more 5′ intervening sequences, and culminating at the promoter. Neither RNA polymerase II (Pol II) nor CBP associated with the inactive gene. During Hoxd4 induction, CBP and RNA Pol II were recruited first to the enhancer and then to the promoter. Whereas the CBP association was transient, RNA Pol II remained associated with both regulatory regions. Histone modification and transcription factor recruitment occurred in posterior, Hox-expressing embryonic tissues, but never in anterior tissues, where such genes are inactive. Together, our observations demonstrate that the direction of histone modifications at Hoxd4 mirrors colinear gene activation across Hox clusters and that the establishment of anterior and posterior compartments is accompanied by the imposition of distinct chromatin states.

scholarly journals Persistent chromatin states, pervasive transcription, and shared cis-regulatory sequences have shaped the C. elegans genome

2019 ◽  
Author(s):  
James M. Bellush ◽  
Iestyn Whitehouse
Keyword(s):  
Mrna Expression ◽  
Histone Modifications ◽  
Open Chromatin ◽  
Regulatory Sequences ◽  
Splice Leader ◽  
Rna Transcription ◽  
Chromatin States ◽  
C Elegans ◽  
Gene Positioning ◽  
Nascent Rna

AbstractDespite highly conserved chromatin states and cis-regulatory elements, studies of metazoan genomes reveal that gene organization and the strategies to control mRNA expression can vary widely among animal species. C. elegans gene regulation is often assumed to be similar to that of other model organisms, yet evidence suggests the existence of distinct molecular mechanisms to pattern the developmental transcriptome, including extensive post-transcriptional RNA control pathways, widespread splice leader (SL) trans-splicing of pre-mRNAs, and the organization of genes into operons. Here, we performed ChIP-seq for histone modifications in highly synchronized embryos cohorts representing three major developmental stages, with the goal of better characterizing whether the dynamic changes in embryonic mRNA expression are accompanied by changes to the chromatin state. We were surprised to find that thousands of promoters are persistently marked by active histone modifications, despite a fundamental restructuring of the transcriptome. We employed global run-on sequencing using a long-read nanopore format to map nascent RNA transcription across embryogenesis, finding that the invariant open chromatin regions are persistently transcribed by Pol II at all stages of embryo development, even though the mature mRNA is not produced. By annotating our nascent RNA sequencing reads into directional transcription units, we find extensive evidence of polycistronic RNA transcription genome-wide, suggesting that nearby genes in C. elegans are linked by shared transcriptional regulatory mechanisms. We present data indicating that the sharing of cis-regulatory sequences has constrained C. elegans gene positioning and likely explains the remarkable retention of syntenic gene pairs over long evolutionary timescales.

scholarly journals Building, testing and distributing common software for the LHC experiments

2019 ◽  
Vol 214 ◽  
pp. 05020
Author(s):  
Javier Cervantes Villanueva ◽  
Gerardo Ganis ◽  
Dmitri Konstantinov ◽  
Grigorii Latyshev ◽  
Pere Mato Vila ◽  
...  
Keyword(s):  
Machine Learning ◽  
Operating Systems ◽  
Automatic System ◽  
Web Pages ◽  
Learning Tools ◽  
Future Directions ◽  
Grid Middleware ◽  
Hardware Architectures ◽  
User Friendly

Building, testing and deploying of coherent large software stacks is very challenging, in particular when they consist of the diverse set of packages required by the LHC experiments, the CERN Beams Department and data analysis services such as SWAN. These software stacks include several packages (Grid middleware, Monte Carlo generators, Machine Learning tools, Python modules) all available for a large number of compilers, operating systems and hardware architectures. To address this challenge, we developed an infrastructure around a tool called lcgcmake. Dedicated modules are responsible for building the packages, con-trolling the dependencies in a reliable and scalable way. The distribution relies on a robust and automatic system, responsible for building and testing the packages, installing them on CernVM-FS and packaging the binaries in RPMs and tarballs. This system is orchestrated through Jenkins on build machines provided by the CERN Openstack facility. The results are published through user-friendly web pages. In this paper we will present an overview of these infrastructure tools and policies. We also discuss the role of this effort within the HEP Software Foundation (HSF). Finally we will discuss the evolution of the infrastructure towards container (Docker) technologies and the future directions and challenges of the project.

Sperm decondensation during fertilisation in the mouse: presence of DNase I hypersensitive sites in situ and a putative role for topoisomerase II

Zygote ◽  
2000 ◽  
Vol 8 (3) ◽  
pp. 197-202 ◽  
Author(s):  
Davide Bizzaro ◽  
Giancarlo Manicardi ◽  
Patrizia Grace Bianchi ◽  
Denny Sakkas
Keyword(s):  
Conformational Changes ◽  
Topoisomerase Ii ◽  
Dnase I ◽  
Dnase I Hypersensitive Sites ◽  
Putative Role ◽  
Hypersensitive Sites ◽  
Dna Alterations ◽  
Sperm Decondensation

In this study our aim was to characterise the presence and the role of DNA alterations during sperm decondensation in the mouse. To visualise the changes during decondensation we investigated for the presence of DNase I hypersensitive sites in situ and for a putative role for topoisomerase II by examining the effect of teniposide, a topoisomerase II inhibitor, during fertilisation. In situ nick translation without the previous addition of DNase I failed to reveal the presence of endogenous nicks in decondensing sperm and pronuclei whereas preincubation of fixed oocytes with DNase I indicated that decondensing sperm were sensitive to this enzyme. Addition of 100 μM teniposide did not completely inhibit pronuclei formation but its addition to the fertilisation medium did lead to the presence of endogenous DNA nicks in decondensing sperm. These observations suggest that DNase I hypersensitivity during sperm decondensation is related to the dramatic conformational changes that the chromatin undergoes during the decondensation process, in which topoisomerase II may be implicated.

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