Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

81 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of chromatin state in Williams-Beuren (WBS), Williams-Beuren Region duplication (WBRdupS), Smith-Magenis (DGS), DiGeorge (DGS) lymphoblastoid cell lines

ABSTRACT: Copy number variants (CNV) influence the expression of genes that map not only within, but also on their flanks. To assess the possible mechanism(s) underlying this “neighboring effect”, we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. We detected alteration of intrachromosomal interactions (chromosomal looping) between the loci of affected genes and the rearranged interval using chromosome conformation capture (4C-seq). These results are consistent with the observed gene expression alterations. We also pinpointed concomitant changes in histone modifications between samples. Modified genes were often looping together, possibly forming an interacting cluster. We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thus possibly modulating expression globally and modifying the phenotype. For example, we observe that the chromatin conformation, histone marks and relative expression levels of the AUTS2 gene, mutations of which are associated with autism and intellectual disabilities, are modified in Williams-Beuren syndrome patients cell lines. Examination of 2 different histone modifications in genomic disorders patients' cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Alexandre Reymond

PROVIDER: E-GEOD-33784 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide maps of chromatin state in Williams-Beuren (WBS), Williams-Beuren Region duplication (WBRdupS), Smith-Magenis (DGS), DiGeorge (DGS) lymphoblastoid cell lines

Project description:Copy number variants (CNV) influence the expression of genes that map not only within, but also on their flanks. To assess the possible mechanism(s) underlying this “neighboring effect”, we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. We detected alteration of intrachromosomal interactions (chromosomal looping) between the loci of affected genes and the rearranged interval using chromosome conformation capture (4C-seq). These results are consistent with the observed gene expression alterations. We also pinpointed concomitant changes in histone modifications between samples. Modified genes were often looping together, possibly forming an interacting cluster. We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thus possibly modulating expression globally and modifying the phenotype. For example, we observe that the chromatin conformation, histone marks and relative expression levels of the AUTS2 gene, mutations of which are associated with autism and intellectual disabilities, are modified in Williams-Beuren syndrome patients cell lines.

2013-11-16 | GSE33784 | GEO

ChipSeq of mouse embryonic fibroblasts from conditional knock-in mouse carrying a phosphorylation-deficient S180A (SA) mutation in exon 5 of the endogenous mouse Trp53 gene locus

Project description:The mouse S180A (SA) mutation of the Trp53 is a p53 phosphorylation-deficient mutant protein with native conformation. Here we want to assess the impact of DNA binding site phosphorylation of the p53 target gene spectrum and transcriptional activity under untreated conditions and following p53 stabilization with the Mdm2 inhibitor nutlin-3a.

2020-06-04 | E-MTAB-9170 | biostudies-arrayexpress

ChipSeq of conditional knock-in mouse carrying the R178E (EE) mutation in exon 5 of the endogenous mouse Trp53 gene locus.

Project description:The mouse R178E (EE) mutation of the Trp53 is a p53 mutant protein with native conformation that lacks the ability to form tetramers and thus constitutes a mutant form of p53 that lacks DNA binding cooperativity. Here we want to assess DNA binding ability of the EE mutant in MEFs under untreated conditions and following p53 stabilization with the Mdm2 inhibitor nutlin-3a and compare it to p53 KO and WT mice.

2019-09-03 | E-MTAB-6793 | biostudies-arrayexpress

Genome-wide distribution of Pbx1/2/3 in mouse cortex at embryonic day 12.5 [ChIP-seq]

Project description:We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/ sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate. Chromatin immunoprecipitation was performed using antibody against Pbx1/2/3/ (sc-888, Santa Cruz). Wild type E12.5 mouse whole cortex was used for the analysis.

2016-02-27 | E-GEOD-78720 | biostudies-arrayexpress

Genome-wide distribution of Pbx1/2/3 in mouse cortex at embryonic day 15.5 [ChIP-seq]

Project description:We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/ sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate. Chromatin immunoprecipitation was performed using antibody against Pbx1/2/3 (sc-888, Santa Cruz). Wild type E15.5 mouse whole cortex was used for the analysis.

2016-03-12 | E-GEOD-79152 | biostudies-arrayexpress

Activation of the Integrated Stress Response by a Jumonji Histone Demethylase Inhibitor Induces Pro-Apoptotic Metabolic Reprogramming in Multiple Myeloma

Project description:Regulation of gene expression by chromatin modification through methylation of histone lysine residues is a dynamic, reversible process that when deregulated is associated with cancer development. In multiple myeloma, combined inhibition of the histone demethylases JARID1B, UTX and JmjD3 by the small molecule GSK-J4 prevents cellular glutamine utilization leading to amino acids deprivation, activates the integrated stress response via GCN2-dependent ATF4 activation, and induces apoptosis. This response is associated with a profound upregulation of metallothionein genes. Combined with clinical data demonstrating that overexpression of JARID1B is associated with shorter survival in multiple myeloma patients, this study highlights histone demethylases as epigenetic drug targets and places this demethylase inhibitor chemotype as having unique potential relative to established anti-myeloma treatment options. In total there are 7 different samples analyzed and one input control. Treatments are carried out with the demethylase inhibitor (or DMSO as negative control) at 6h and 48h, or with LNA targeting demethylases (or scrambled LNA) at 7 days. A negative control at 0h is included.

2015-08-21 | E-GEOD-60626 | biostudies-arrayexpress

BolA is a transcriptional switch that turns off motility and turns on biofilm development (ChIP-seq)

Project description:Bacteria are extremely versatile organisms which rapidly adapt to changing environments. When Escherichia coli cells switch from planktonic growth to biofilm, flagellum formation is turned off, and the production of fimbriae and extracellular polysaccharides is switched on. Here we show that BolA protein is a new bacterial transcription factor which modulates the switch from planktonic to sessile lifestyle. BolA negatively modulates flagella biosynthesis and thus swimming capacity. Furthermore, BolA overexpression favors biofilm formation and involvesinvolving fimbriae-like adhesins and curli production. Our results unraveled for the first time that BolA is a protein with high affinity to DNA, involved in the regulation of several genes of E. coli at a genome-wide scale level. Moreover, this observation further demonstrated that the most significant targets of this protein involved a complex network of genes encoding proteins extremely necessary in biofilm development processes. Herein we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation process. In the study presented here DNA enrichment was analyzed in 2 different strains, a strain containing bolA-3xflag-tag and a deletion mutant for this gene, which was used as the control sample.

2015-02-19 | E-GEOD-58623 | biostudies-arrayexpress

Efficient immortalization of normal human mammary epithelial cells using two pathologically relevant agents does not require gross genomic alterations

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-03 | E-GEOD-48504 | biostudies-arrayexpress

The histone chaperone CAF-1 safeguards somatic cell identity during transcription factor-induced reprogramming (sequencing)

Project description:During development, specialized cell lineages are generated through the establishment of cell type-specific transcriptional patterns and epigenetic programs. However, the precise mechanisms and regulators that maintain these specialized cell states remain largely elusive. To identify molecules that safeguard somatic cell identity, we performed two comprehensive RNAi screens targeting known and predicted chromatin regulators during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Remarkably, subunits of the chromatin assembly factor-1 (CAF-1) complex emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation, DNA methylation and heterochromatin maintenance. Suppression of CAF-1 increased reprogramming efficiencies by several orders of magnitude and generated iPSCs two to three times faster compared to controls without affecting cell proliferation. We demonstrate that suppression of CAF-1 leads to a more accessible chromatin structure specifically at enhancer elements early during reprogramming. These changes were accompanied by increased binding of the reprogramming factor Sox2 to ESC-specific regulatory elements and earlier activation of pluripotency-associated genes. Notably, suppression of CAF-1 also enhanced iPSC formation from blood progenitors as well as the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 as an unanticipated regulator of somatic cell identity and provide a potential strategy to modulate cellular plasticity in a regenerative setting. Keywords: Genome binding/occupancy profiling by high throughput sequencing Chromatin accessibility and Sox2 bindings in CAF-1 knockdown and Renilla control during early OKSM reprogramming by high throughput sequencing

2015-12-10 | E-GEOD-72744 | biostudies-arrayexpress

miRNA genes in HMEC and HMF

Project description:This SuperSeries is composed of the following subset Series: GSE28374: DNA methylation of miRNA genes in HMEC and HMF GSE28375: Histone H3 acetylation of miRNA genes in HMEC and HMF GSE28376: Histone H3 lysine 27 trimethylation of miRNA genes in HMEC and HMF GSE28377: Histone H3 lysine 4 trimethylation of miRNA genes in HMEC and HMF GSE28378: Histone H3 lysine 9 dimethylation of miRNA genes in HMEC and HMF Refer to individual Series

2011-04-05 | E-GEOD-28380 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data