Domains of genomewide gene expression dysregulation in Down syndrome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Audrey Letourneau
PROVIDER: E-GEOD-55426 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Trisomy 21 (T21) is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in T21, and to eliminate the noise of the genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for T21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either up- or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twinsM-bM-^@M-^Y fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of DS and wild-type, also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall LADs position was not altered in trisomic cells. However, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results suggest that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome and that GEDDs may therefore contribute to some T21 phenotypes. LaminB1-chromatin interactions in a pair of monozygotic twins discordant for trisomy21
2014-04-08 | E-GEOD-55289 | biostudies-arrayexpress
Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. LaminB1-chromatin interactions were assayed in human HT1080 cells by induction of Dam_LMNB1 expression in a stable cell line with shield1.
2013-01-31 | E-GEOD-40094 | biostudies-arrayexpress
Project description:Regulation of gene expression is highly conserved between vertebrates, yet the genomic binding patterns of transcription factors are poorly conserved, suggesting that other mechanisms may contribute. The spatial organization of chromosomes in the nucleus is known to affect gene activity, but it is unclear to what extent this organization is conserved in evolution. Genome-wide maps of nuclear lamina (NL) interactions show that human and mouse chromosomes have highly similar folding patterns inside the nucleus. Breaks in synteny are often located at transition points between NL interacting and intra-nuclear regions. Data were compared against data from Peric-Hupkes, Meuleman et al. (Molecular Cell, 2010). LaminB1-chromatin interactions were assayed in human ESCs and human HT1080 cells. LaminA-chromatin interactions were assayed in human HT1080 cells. For the all samples there were 2 biological replicates, that were hybridized in a dye-swap design.
2012-10-10 | E-GEOD-22428 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-01-31 | E-GEOD-40112 | biostudies-arrayexpress
Project description:The three-dimensional organization of chromosomes within the nucleus and its dynamics during differentiation are largely unknown. We present a genome-wide analysis of the interactions between chromatin and the nuclear lamina during differentiation of mouse embryonic stem cells (ESCs) into lineage-committed neural precursor cells (NPCs) and terminally differentiated astrocytes. Chromatin in each of these cell types shows a similar organization into large lamina associated domains (LADs), which represent a transcriptionally repressive environment. During sequential differentiation steps, lamina interactions are progressively modified at hundreds of genomic locations. This remodeling is typically confined to individual transcription units and involves many genes that determine cellular identity. From ESCs to NPCs, the majority of genes that move away from the lamina are concomitantly activated. Strikingly, a significant amount remain inactive yet become primed for activation by further differentiation. These results suggest that lamina-genome interactions are widely involved in the control of gene expression programs during lineage commitment and terminal differentiation. laminB1-chromatin interactions were assayed in 4 different mouse cell-types. For each cell-type there were 2 biological replicates, that were hybridized in a dye-swap design.
2010-05-27 | E-GEOD-17051 | biostudies-arrayexpress
Project description:The nuclear lamina (NL) is a filamentous layer lining the inner-nuclear-membrane (INM) that aids in the organization of the genome in large domains of low transcriptional activity. Recently, it was shown that the single-cell genome-NL interactions are much more dynamic than previously anticipated, which challenges the concept of the NL as a safe guard for transcriptional repressed genes. Here we discuss the role of the NL in light of these new findings and introduce Lamin A and BAF as potential modulators of LAD positioning BAF-chromatin and Lamin B2-chromatin interactions were assayed in human HT1080 by DamID on Nimblegen microarrays, with two biological replicates each, that were hybridized in a dye-swap design.
2014-02-15 | E-GEOD-55066 | biostudies-arrayexpress
Project description:Developmental gene expression results from the orchestrated interplay between genetic and epigenetic mechanisms. Here, we describe upSET, a transcriptional regulator encoding a SET domaincontaining protein recruited to active and inducible genes in Drosophila. However, unlike other Drosophila SET proteins associated with gene transcription, UpSET is part of an Rpd3/Sin3-containing complex that restricts chromatin accessibility and histone acetylation to promoter regions. In the absence of UpSET, active chromatin marks and chromatin accessibility increase and spread to genic and flanking regions due to destabilization of the histone deacetylase complex. Consistent with this, transcriptional noise increases, as manifest by activation of repetitive elements and off-target genes. Interestingly, upSET mutant flies are female sterile due to upregulation of key components of Notch signaling during oogenesis. Thus UpSET defines a class of metazoan transcriptional regulators required to fine tune transcription by preventing the spread of active chromatin. For determining DamID based UpSET chromatin profile, three biological replicates were used. For evaluating chromatin accessibility, two biological replicates were performed.
2012-12-07 | E-GEOD-34718 | biostudies-arrayexpress
Project description:Laminopathies are caused by mutations in components of the nuclear envelope (NE). While most NE components are widely expressed, laminopathies affect only a subset of tissues. However, the understanding of the molecular mechanisms that explain this phenomenon is still elusive. Here we have performed a genome wide DamID analysis in adult C. elegans nematodes comparing the DNA association profile of two components of the NE, Lamin/LMN-1 and Emerin/EMR-1. Although both proteins were associated to silent DNA, EMR-1 showed a predominant role in the anchoring of muscle and neuronal promoters to the nuclear periphery. Deletion of either EMR-1 or LEM-2, another integral NE protein, caused local changes in nuclear architecture with both increased and decreased LMN-1 association. Comparison of Dam::LMN-1 and Dam::EMR-1 DNA assotiation in wild type strains and Dam::LMN-1 DNA association in wild type, lem-2(tm1582) and emr-1(gk119) mutant backgrounds.
2013-12-02 | E-GEOD-44188 | biostudies-arrayexpress
Project description:We made Polycomb (PC) and histone H3 lysine 27 trimethylation (H3K27me3) chromatin binding maps in central brain tissue from 3rd instar larvae, allowing us to make a direct comparison to our 4C data (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23166). Our results demonstrate that our PC and H3K27me3 maps are highly similar, and fit with previously identified hallmarks of PcG-bound chromatin, namely: PC and H3K27me3 co-occur in the genome as large contiguous domains that largely repress transcription of the underlying genes, which encode important regulators of development. Keywords: Genome binding/occupancy profiling by genome tiling array DamID experiments for Polycomb were performed in Drosophila larval brain tissue. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing.
2011-12-31 | E-GEOD-23298 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2012-12-07 | E-GEOD-34720 | biostudies-arrayexpress