Heterochromatin Protein 1 (HP1) is a major regulator of chromatin structure and function. In animals, the network of proteins interacting with HP1 is mainly associated with constitutive heterochromatin marked by H3K9me3. HP1 physically interacts with the putative orthologue of the SNF2 chromatin remodeler ATRX, which controls deposition of the histone variant H3.3 in mammals. In Arabidopsis thaliana, we show that the orthologue of ATRX participates in H3.3 deposition and characterize the function of conserved domains of plant ATRX. We show that the plant Like HP1 (LHP1) interacts with ATRX through domains that evolved specifically in land plants ancestors. Interaction between ATRX and LHP1 affects the expression of a limited subset of genes controlled by the POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), including the flowering time regulator FLC. In the context of flowering time, ATRX function requires the novel LHP1-interacting domain and the ATPase of the ATRX SNF2 helicase. We conclude that distinct evolutionary pathways led to interaction between ATRX and HP1 in mammals or its counterpart LHP1 in plants, resulting in distinct modes of transcriptional regulation. Overall design: 1 sample (mutant) + 1 reference sample (control)
LHP1 Interacts with ATRX through Plant-Specific Domains at Specific Loci Targeted by PRC2.
Age, Specimen part, Subject
View SamplesTrascriptome analysis of osteosarcoma samples were performed Overall design: Tumor samples were obtained from a previously published Sleeping Beauty forward genetic screen, cell lines were derived from previous primary tumors and sequenced using Illumina HiSeq 2000
Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in Osteosarcoma.
Specimen part, Cell line, Subject
View SamplesThree normal human osteoblast samples, acquired from PromoCell, were used as controls to compare to RNA-seq data from prepublished osteosarcoma samples (submitted to the European Bioinformatics Institute; EGAS00001000263) for the purpose of evaluating expression levels of genes identified as common insertions sites in a Sleeping Beauty screen of osteosarcomas in mice. Overall design: Three normal human osteoblast samples (pellet form in RNAlater) were acquired from PromoCell (Heidelberg, Germany), and RNA was isolated from them immediately upon receipt.
A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis.
No sample metadata fields
View SamplesOver-activation of the aryl hydrocarbon receptor by TCDD in mice leads among other phenotypes to a severe thymic atrophy accompanied by immunosuppression. TCDD causes a block in thymocyte maturation and a preferential emigration of immature CD4-CD8- DN thymocytes (recent thymic emigrants) into the periphery. As part of this study gene expression profiles from DN thymocytes and thymic emigrants were generated from TCDD and solvent control mice
Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo.
Specimen part, Treatment
View SamplesWe report the application of RNA-seq analysis for high-throughput profiling of murine lungs infected with Aspergillus fumigatus. We compared the lung transcription of wildtype murine lungs and lungs from mice deficient in metabolic cytokine adiponectin. Overall design: Examination of 2 different mice strain and comparison of lung transcripts in response to Aspergillus fumigatus infection.
The Metabolic Cytokine Adiponectin Inhibits Inflammatory Lung Pathology in Invasive Aspergillosis.
Specimen part, Cell line, Subject
View SamplesPost-translational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of genes expressed. Gene ontology analysis revealed that PARP could exert these effects through transcription factors and chromatin-remodeling enzymes, including the Polycomb Repressive Complex 2 (PRC2) member EZH2. EZH2 mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a modification associated with chromatin compaction and gene silencing. Both pharmacological inhibition of PARP and knockdown of PARP1 induced the expression of EZH2 that resulted in increased global H3K27me3. Chromatin immunoprecipitation confirmed that PARP1 inhibition led to H3K27me3 deposition at EZH2-target genes, which resulted in gene silencing. Moreover, increased EZH2 expression is attributed to occupancy loss of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition. Together, these data show that PARP plays an important role in global gene regulation and identifies for the first time a direct role of PARP1 in regulating the expression and function of EZH2. Overall design: Examination of the effect of PARP inhibition on global gene expression in LCLs cell lines. mRNA profiles of LCLs cells lines treated at different time points with olaparib were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2.
No sample metadata fields
View SamplesCD4+ T cells from 8-12 week female mice were isolated from wt and AhR-/- mice 24h after injection of 10g/kg TCDD or solvent control.
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View SamplesEffect of an immunosupressive dose of TCDD, a ligand for the aryl hydrocarbon receptor, on the gene expression profile of fetal DN thymocytes and thymic emigrants
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Specimen part, Treatment
View SamplesThe aim of the study was to illucidate how BAFF mediates B cell survival and growth through the identification of BAFF-regulated genes.
BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism.
No sample metadata fields
View Samples8-12 week, female C57BL/6 mice were injected with 10 g/kg TCDD or solvent control. CD8+ T cells from spleen were FACS purified and submitted to transcription profiling
Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.
Sex, Treatment
View Samples