Project description:Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. This represents the human CD34 ChIP-seq portion of this dataset. Human hematopoietic cells were cross-linked with formaldehyde for 20 min. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. A sample of whole cell extract (WCE) was sequenced and used as the background to determine enrichment. ChIP was performed using an antibody against total Smad1 (Santa Cruz SC-7965), Tcf7l2 (Santa Cruz SC-8631),Gata1 (Santa Cruz SC-265), Gata2 (Santa Cruz SC-9008) or CEBPA (SC-9314).
Project description:The oncogenic transcription factor TAL1/SCL is aberrantly overexpressed in over 40% of cases of T-cell acute lymphoblastic leukemia (T-ALL), emphasizing the importance of the TAL1-regulated transcriptional program in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, GATA3, ETS1 and RUNX1 in T-ALL cells. We find that TAL1 forms an interconnected auto-regulatory loop with its partners, which contributes to the sustained upregulation of its direct target genes. Importantly, we also find the MYB oncogenic transcription factor is directly activated by the TAL1 complex and positively regulates many of the same target genes, thus forming a feed-forward positive regulatory loop that further promotes the TAL1-regulated oncogenic program. Human T-ALL cells were cross-linked with formaldehyde for 20 min. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. A sample of whole cell extract (WCE) was sequenced and used as the background to determine enrichment. ChIP was performed using an antibody against total TAL1 (Santa Cruz SC-12984), TCF12/HEB (Santa Cruz SC-357),TCF3/E2A (Santa Cruz SC-349X), LMO1 (Santa Cruz SC-10494), LMO2 (R&D Systems AF2726), GATA3 (Santa Cruz SC-22206) and RUNX1 (Santa Cruz SC-8563). This represents the ChIP-seq portion of this dataset. Human Jurkat cells were cross-linked with formaldehyde for 20 min. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. A sample of whole cell extract (WCE) was sequenced and used as the background to determine enrichment. ChIP was performed using an antibody against total TAL1 (Santa Cruz SC-12984), TCF12/HEB (Santa Cruz SC-357),TCF3/E2A (Santa Cruz SC-349X), LMO1 (Santa Cruz SC-10494), GATA3 (Santa Cruz SC-22206) and RUNX1 (Santa Cruz SC-8563). This represents the ChIP-seq portion of this dataset.
Project description:Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. This represents the human ChIP-seq portion of this dataset on leukemia cell lines. Human hematopoietic cells were cross-linked with formaldehyde for 20 min. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. A sample of whole cell extract (WCE) was sequenced and used as the background to determine enrichment. ChIP was performed using an antibody against total Smad1 (Santa Cruz SC-7965), Tcf7l2 (Santa Cruz SC-8631),Gata1 (Santa Cruz SC-265), Gata2 (Santa Cruz SC-9008), CEBPA (SC-9314) or H3K4me1 (Abcam ab8895).
Project description:Binding of HDAC2 and HDAC3 was assayed using antibodies SC-7899x and SC-11417x examination of HDAC2 and HDAC3 binding in rat neural stem cells
Project description:<p>Ulcerative colitis (UC) involves epithelial injury, gut microbial dysbiosis, disturbed microbial metabolism, and mucosal inflammation. This study evaluated the protective effect of Schisandra chinensis (SC) against dextran sulfate sodium (DSS)-induced UC and investigated the underlying microbiota–metabolite–host signaling mechanism. UPLC-Q-TOF-MS/MS identified 38 constituents in SC, predominantly lignans, organic and phenolic acids, and terpenoids. SC reduced body weight loss, disease activity, colon shortening, mucosal and histological injury, and pro-inflammatory cytokine levels, while partially restoring claudin-1 and occludin expression. Metagenomic analysis showed that SC restructured the DSS-disrupted microbiota, enriched Parabacteroides goldsteinii, and increased the predicted abundance of pathways related to valine, leucine, and isoleucine degradation. Untargeted metabolomics and targeted fatty acid analysis showed lower fecal leucine and higher isovalerate levels after SC treatment. Whole-colon transcriptomic and western blot analyses further demonstrated that SC suppressed the mTOR/HIF-1α/STAT3/IL-17 inflammatory program in colonic tissue. Antibiotic pretreatment weakened several protective effects of SC, whereas P. goldsteinii or sodium isovalerate administration partially recapitulated its anti-inflammatory and barrier-restorative effects. Conversely, the mTOR activator MHY1485 attenuated SC-mediated protection. These findings indicate that the protective effects of SC are associated with remodeling of a P. goldsteinii-related leucine–isovalerate metabolic network and attenuation of colonic mTOR/HIF-1α/STAT3/IL-17 signaling. This study provides a microbiota-centered mechanistic basis for the therapeutic potential of SC in UC.</p>