RNA-seq of resting and activated CD4+ T cells +-JQ1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE122735 | GEO | 2018/11/21
REPOSITORIES: GEO
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Project description:HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are delineated with super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional activity are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
2019-08-21 | GSE134382 | GEO
Project description:HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional status are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
2018-11-22 | GSE122826 | GEO
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2024-03-12 | GSE243675 | GEO
Project description:Large-genome bacteriophages (jumbo phages) of the Chimalliviriadae family assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and CRISPR/Cas nucleases. While the nuclear shell provides broad protection against host nucleases, it necessitates transport of mRNA out of the nucleus-like compartment for translation by host ribosomes, and transport of specific proteins into the nucleus-like compartment to support DNA replication and mRNA transcription. Here we identify a conserved phage nuclear shell-associated protein that we term Chimallin C (ChmC), which adopts a nucleic acid-binding fold, binds RNA with high affinity in vitro, and binds phage mRNAs in infected cells. ChmC also forms phase-separated condensates with RNA in vitro. Targeted knockdown of ChmC using mRNA-targeting dCas13d halts infections at an early stage. Taken together, our data suggest that the conserved ChmC protein acts as a chaperone for phage mRNAs, potentially stabilizing these mRNAs and driving their translocation through the nuclear shell to promote translation and infection progression.
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Project description:The human immunodeficiency virus (HIV) enters the nucleus to establish infection, but the role of nuclear envelope proteins in this process is incompletely understood. Inner nuclear transmembrane proteins SUN1 and SUN2 connect nuclear lamins to the cytoskeleton and participate in the DNA damage response (DDR). Increased levels of SUN1 or SUN2 potently restrict HIV infection through an unresolved mechanism. Here, we find that the antiviral activities of SUN1 and SUN2 are distinct. HIV-1 and HIV-2 are preferentially inhibited by SUN1 and SUN2, respectively. We identify DNA damage inducers that stimulate HIV-1 infection and show that SUN1, but not SUN2, neutralizes this effect. Finally, we show that chromatin movements and nuclear rotations are associated with the effects of SUN proteins and Lamin A/C on infection. These results reveal an emerging role of chromatin dynamics and the DDR in the control of HIV infection by structural components of the nuclear envelope.
2022-03-16 | GSE162019 | GEO
Project description:<p>Nucleic acid and histone modifications critically depend on tricarboxylic acid (TCA) cycle for substrates and co-factors. Although a few TCA cycle enzymes have been reported in the nucleus, the corresponding pathways are considered to operate in mitochondria. Here, we show that a part of the TCA cycle is operational also in the nucleus. Using 13C-tracer analysis, we identified activity of glutamine-to-fumarate, citrate-to-succinate, and glutamine-to-aspartate routes in the nuclei of HeLa cells. Proximity labeling mass-spectrometry revealed a spatial vicinity of the involved enzymes with core nuclear proteins. We further show nuclear localization of aconitase 2 and 2-oxoglutarate dehydrogenase in mouse embryonic stem cells. Nuclear localization of the latter enzyme, which produces succinyl-CoA, changed from pluripotency to differentiated state with accompanying changes in the nuclear protein succinylation. Together, our results demonstrate operation of an extended metabolic pathway in the nucleus warranting a revision of the canonical view on metabolic compartmentalization.</p>
2022-06-15 | MTBLS2235 | MetaboLights
Project description:The mantle is a thin tissue from which proteins are secreted dictating the mollusk shell construction. As a conserved organ involved in shell formation throughout mollusks, the mantle is an excellent foundation from which to study biomineralization. A P. maxima mantle tissue specific cDNA microarray, termed PmaxArray 1.0, has been developed comprising 5000 cDNA transcripts derived from the mantle tissue of P. maxima. This tool has been used to investigate the spatial functional dynamics of the mantle tissue identifying over 2000 PmaxArray 1.0 spots as differentially expressed spatially within this organ. Gene expression profiles observed for these transcripts indicated 5 major spatial functions for the mantle, 3 of which have been putatively attributed to shell formation roles associated with nacre microstructure, calcite prismatic microstructure and periostracum. These transcripts are further examined with in situ expression localization and comparative sequence analyses in reference to potential shell formation roles. This spatial investigation has expedited the elucidation of functions within the dynamic mantle organ, paying particular attention to of shell biomineralization. Keywords: Spatial expression profiling by array
2010-02-05 | GSE14303 | GEO
Project description:The mantle is a thin tissue from which proteins are secreted dictating the mollusk shell construction. As a conserved organ involved in shell formation throughout mollusks, the mantle is an excellent foundation from which to study biomineralization. A P. maxima mantle tissue specific cDNA microarray, termed PmaxArray 1.0, has been developed comprising 5000 cDNA transcripts derived from the mantle tissue of P. maxima. This tool has been used to investigate the spatial functional dynamics of the mantle tissue identifying over 2000 PmaxArray 1.0 spots as differentially expressed spatially within this organ. Gene expression profiles observed for these transcripts indicated 5 major spatial functions for the mantle, 3 of which have been putatively attributed to shell formation roles associated with nacre microstructure, calcite prismatic microstructure and periostracum. These transcripts are further examined with in situ expression localization and comparative sequence analyses in reference to potential shell formation roles. This spatial investigation has expedited the elucidation of functions within the dynamic mantle organ, paying particular attention to of shell biomineralization. Keywords: Spatial expression profiling by array The mantle tissue from 9 animals was dissected into 5 separate sections: outer fold (OF), middle fold (MF), inner fold (IF), ventral mantle tissue (VM) and dorsal mantle tissue (DM). Total RNA was extracted from these tissues and pooled across subjects in order to reduce the effect of biological variation; such that 3 individuals were pooled together totaling 3 pooled replicate samples for each tissue. All the biologically pooled tissue types were compared against a common reference in which total RNA from all tissues types and all nine animals was equally pooled. A total of 30 dual channel microarrays hybridizations were performed and analyzed.
2010-05-15 | E-GEOD-14303 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE10697: Self-Self Hybridisation were used to set confidence 99% intervals GSE10698: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 1 GSE10699: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 2 Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10701 | biostudies-arrayexpress