The M1 and the M2 macrophage polarization programs (activated by IFN? and IL-4, respectively) lie at the opposite edges of a continuum of activation states but are frequently co-activated during co-infections and in cancer despite controlling divergent functional responses. Whether these two programs are mutually exclusive, how they influence each other, and whether one represents the prevailing response, are all open questions. Co-administration of IFN? and IL-4 exerted complex inhibitory effects over the M1 and M2 programs at the level of both epigenomic and transcriptional changes. Computational data mining and validation analyses revealed the molecular basis of the differential sensitivity of genes and cis-regulatory elements to the antagonistic effects of the opposite stimulus. For instance, while STAT1 and IRF motifs were associated with robust and IL-4-resistant responses to IFN?, their coexistence with binding sites for some auxiliary transcription factors such as AP-1, generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation and the starting point for understanding macrophage responses in complex environmental conditions Overall design: Analysis of transcriptional and epigenomic changes in mouse macrophages stimulated with different cytokines or their combinations
Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.
Specimen part, Cell line, Treatment, Subject
View SamplesThe 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.
High constitutive activity of a broad panel of housekeeping and tissue-specific <i>cis</i>-regulatory elements depends on a subset of ETS proteins.
Specimen part, Cell line, Treatment, Subject
View SamplesUpon 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.
Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination.
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View SamplesIn GnRH-antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression
In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression.
No sample metadata fields
View SamplesCONTEXT Nowadays, the molecular mechanisms involved in endometrial receptivity and implantation are still not clear.
Cyclooxygenase-2 network as predictive molecular marker for clinical pregnancy in in vitro fertilization.
No sample metadata fields
View SamplesInfluence of ovarian stimulation with 200 IU of hCG, (administered in the late follicular phase among ICSI patients undergoing a GnRH-antagonist protocol), on the endometrium on the day of oocyte pick-up.
Cyclooxygenase-2 network as predictive molecular marker for clinical pregnancy in in vitro fertilization.
Specimen part
View SamplesKarrikins promote seed germination in Arabidopsis thaliana. Completion of germination (protrusion of the radicle) is not observed until ~72 h in dormant wildtype seed under these conditions. We used microarrays to examine karrikin-induced transcriptional changes after 24 h of imbibition. Transcriptional changes may indicate events leading to karrikin-induced germination or karrikin-specific markers.
Karrikins enhance light responses during germination and seedling development in Arabidopsis thaliana.
Specimen part, Treatment
View SamplesCurcumin is a potent anti-inflammatory compound capable of preventing chemically induced colitis in mice.
Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent.
Treatment
View SamplesNa+/H+ exchanger 3 (NHE3) provides a major route for intestinal Na+ absorption. It has been considered as a target of proinflammatory cytokines and enteropathogenic bacteria and impaired NHE3 expression and/or activity may be responsible for inflammation-associated diarrhea.
Colonic gene expression profile in NHE3-deficient mice: evidence for spontaneous distal colitis.
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View SamplesHepatic gene expression analysis in mice fed control diet or diets supplemented with 1% Fraction 1 (haxane) or Fraction 2 (methanol) of Boswellia Serrata
Effects of Boswellia serrata in mouse models of chemically induced colitis.
No sample metadata fields
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