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Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1MLL4) whose specific functions are largely unknown. By using a genomic approach, we found that in macrophages, MLL4 (also known as Wbp7) was required for the expression of Pigp, an essential component of the GPI-GlcNAc transferase, the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor synthesis. Impaired Pigp expression in Wbp7-/- macrophages abolished GPI anchor-dependent loading of proteins on the cell membrane. Consistently, loss of GPI-anchored CD14, the coreceptor for lipopolysaccharide (LPS)
Publication Title
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pan-Hdac inhibitors (HDACi) are endowed with a potent anti-inflammatory activity, but the relative role of each of the eleven Hdac proteins sensitive to HDACi to the inflammatory gene expression program is unknown. Using an integrated genomic approach we found that Hdac3-deficient macrophages are unable to activate almost half of the inflammatory gene expression program when stimulated with lipopolysaccharide (LPS). A large part of the activation defect is due to loss of basal and LPS-inducible expression of IFNb, which in basal cells maintains Stat1 protein levels, and after stimulation acts in an autocrine/paracrine manner to promote a secondary wave of Stat1-dependent gene expression. We show that loss of Hdac3-mediated repression of nuclear receptors leads to hyperacetylation of thousands of genomic sites and associated gene derepression. The upregulation of the constitutively expressed prostaglandin endoperoxide synthase, Ptgs1 (Cox-1), has a causative role in the phenotype, since its chemical inhibition reverts the Ifnb activation defect. These data may have relevance for the use of selective Hdac inhibitors as anti-inflammatory agents.
Publication Title
Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The genomic repertoire of enhancers and promoters that control the transcriptional output of terminally differentiated cells includes cell type-specific and housekeeping elements. Whether the constitutive activity of these two groups of cis-regulatory elements relies on entirely distinct or instead shared regulators is unknown. By dissecting the cis-regulatory repertoire of macrophages, we found that the ELF subfamily of ETS proteins selectively bound within 60 bp from the transcription start sites of highly active housekeeping genes. ELFs also bound constitutively active, but not poised macrophage-specific enhancers and promoters. The role of ELFs in promoting constitutive transcription is suggested by multiple evidences: ELF sites enabled transcriptional activation by endogenous and minimal synthetic promoters; ELF recruitment was stabilized by the transcriptional machinery, and ELF proteins mediated recruitment of transcriptional and chromatin regulators to core promoters. These data indicate that a distinct subfamily of ETS proteins imparts high transcriptional activity to a broad range of housekeeping and tissue-specific cis-regulatory elements, which is consistent with the role of an ETS family ancestor in core promoter regulation in a lower eukaryote. Overall design: Nascent RNA sequencing of primary bone marrow-derived macrophages (BMDM) This series contains a re-analysis of GSM1880858 from GSE73021. The file MacroTFs_171-genes.fpkm_tracking.gz contains the FPKM values for this sample.
Publication Title
High constitutive activity of a broad panel of housekeeping and tissue-specific <i>cis</i>-regulatory elements depends on a subset of ETS proteins.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol_II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adapter protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1/COMPASS H3K4 methyltransferase and the nuclear Protein Phosphatase 1 (PP1) complexes to the initiating Pol_II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1 or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes, active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs. Overall design: polyA-mRNAs or 4sU-labeled RNAs from BMDMs, either untreated or treated for with lipopolysaccharide (LPS) for the indicated time. Experiments were carried out in cells containing either a short hairpin targeting either of these: 1) Wdr82; 2) Set1a+Set1b; 3) Pnuts; or the empty vector (LMP) or a scrambled as a control. When specified, cells were pre-treated with 5,6-Dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB) in order to prevent RNA polymerase II elongation.
Publication Title
Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Fibro-adipogenic progenitors (FAPs) are emerging cellular components of the skeletal muscle regenerative environment. The alternative functional phenotype of FAPs - either supportive of muscle regeneration or promoting fibro-adipogenic degeneration - is a key determinant in the pathogenesis of muscular diseases, including Duchenne Muscular Dystrophy (DMD). However, the molecular regulation of FAPs is still unknown. We show here that an "HDAC-myomiR-BAF60 variant network" regulates the functional phenotype of FAPs in dystrophic muscles of mdx mice. Combinatorial analysis of gene expression microarray and genome-wide chromatin remodeling by Nuclease accessibility (NA)-seq revealed that HDAC inhibitors de-repress a "latent" myogenic program in FAPs from dystrophic muscles at early stages of disease progression. In these cells HDAC inhibition promoted the expression of two core components of the myogenic transcriptional machinery, MyoD and BAF60C, and upregulated the myomiRs (miRs) miR-1.2, miR-133 and miR-206, which target two alternative BAF60 variants (BAF60A and B) ultimately leading to the activation of a pro-myogenic program at the expense of the fibro-adipogenic phenotype. By contrast, FAPs from dystrophic muscles at late stages of disease progression displayed resistance to HDACi-induced chromatin remodeling at myogenic loci and fail to activate the pro-myogenic phenotype. These results reveal a previously unappreciated disease stage-specific bipotency of mesenchimal cells within the regenerative environment of dystrophic muscles. Resolution of such bi-potency by epigenetic interventions, such as HDACi, provides the molecular rationale for the in situ reprogramming of target cells to promote therapeutic regeneration of dystrophic muscles. Overall design: miRNA modulation upon Histone Deacetylase inhibition in Fibro-Adipogenic Progenitors (FAPs) derived from young mdx mice was evaluated by small RNA-sequencing in 2 controls and 2 treated samples
Publication Title
HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibro-adipogenic progenitors in dystrophic muscles.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
CD133 (Prominin1) is pentaspan transmembrane glycoprotein expressed in several stem cell populations and cancers. Reactivity with an antibody (AC133) to a glycoslyated form of CD133 has been widely used for the enrichment of cells with tumor initiating activity in xenograph transplantation assays. We have found by fluorescence-activated cell sorting that increased AC133 reactivity in human embryonic stem cells, colon cancer and melanoma cells is correlated with increased DNA content and reciprocally, that the least reactive cells are in the G1/G0 portion of the cell cycle. Continued cultivation of cells sorted on the basis of high and low AC133 reactivity results in a normalization of the cell reactivity profiles indicating that cells with low AC133 reactivity can generate highly reactive cells as they resume proliferation. The association of AC133 with actively cycling cells may contribute to the basis for enrichment for tumor initiating activity.
Publication Title
Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Gene expression profiling of the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminence, and cerebral cortex (CTX) at various embryonic stages (E12.5, E14 and E16).
Publication Title
Comprehensive spatiotemporal transcriptomic analyses of the ganglionic eminences demonstrate the uniqueness of its caudal subdivision.
Sample Metadata Fields
Sex, Specimen part
View Samples
GSE1584- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mouse erythroid progenitors (EP) in comparison to granulocyte/monocyte - macrophage progenitors (GMP) from 10 - 16 week old C57/Bl6 - S129Ola (mixed genetic background) purified by flow cytometry
Publication Title
Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E).
Sample Metadata Fields
No sample metadata fields
View Samples