Regulation of genes by HDAC2 via enzyme activity-independent manner during HL-60 cell differentiation by TPA
Ontology highlight
ABSTRACT: Human myeloid leukemia cell line, HL-60 cells, have a potential to differentiate into monocytes with treatment of 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the underlying mechanism of differentiation by TPA is not fully elucidated yet. Here, we performed ChIP-seq profiling using RNA Pol II, HDAC2, AcH3 and H3K27me3, and analyzed the differential chromatin state changes during HL-60 differentiation by TPA. In this study, we focused on the atypical active genes, which showed enhanced H3 acetylation occupancies despite increased HDAC2 recruitment. We found that HDAC2 regulates the expression of these genes positively via histone deacetylase activity-independent manner. HDAC2 interacted and recruited Paired Box 5 (PAX5) to promoter of the target genes and regulated PAX5-mediated gene activation. Taken together, these data demonstrated the profiling of differentiation specific-chromatin status during the differentiation in HL-60 cells by TPA and suggested that HDAC2 activates certain genes through the interaction with PAX5 in enzyme activity independent pathway.
Project description:Human primary keratinocytes were left untreated or treated for 48 hr with 12-O-tetradecanoylphorbol-13-acetate (TPA) and expression profiles were compared to find long ncRNAs expressed and differentially regulated upon differentiation.
Project description:Human primary keratinocytes were left untreated or treated for 48 hr with 12-O-tetradecanoylphorbol-13-acetate (TPA) and expression profiles were compared to find long ncRNAs expressed and differentially regulated upon differentiation. 4 replicates of minus TPA and 3 of plus TPA with dye-swap. Custom-made microarray from Agilent.
Project description:The aim was to demonstrate that pretreatment with RGRN-305 suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced alterations in gene expression.
Project description:12-O-tetradecanoylphorbol-13-acetate (TPA) promotes skin carcinogenesis. CDDO is a potential antioxidative and antiinflammatory agent to prevent the TPA-induced skin cell transformation at nanomolar scale. We characterized the transcriptome, CpG methylome, and pathway network of JB6 cells treated with TPA and TPA + CDDO using RNA sequencing, methyl sequencing, and QIAGEN Ingenuity Pathway Analysis.
Project description:12-O-tetradecanoylphorbol-13-acetate (TPA) promotes skin carcinogenesis. CDDO is a potential antioxidative and antiinflammatory agent to prevent the TPA-induced skin cell transformation at nanomolar scale. We characterized the transcriptome, CpG methylome, and pathway network of JB6 cells treated with TPA and TPA + CDDO using RNA sequencing, methyl sequencing, and QIAGEN Ingenuity Pathway Analysis.
Project description:We report that P2ry6-deficient mice exhibit marked resistance to 7,12-dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin papilloma formation compared with wild-type mice. Consistent with these findings, epidermal hyperplasia in response to TPA stimulation was suppressed in the P2ry6 knockout or MRS2578 (P2RY6 antagonist)-treated mice. The dramatic decrease in hyperplasia and tumorigenesis due to P2ry6 disruption was associated with the suppression of TPA-induced keratinocyte proliferation and inflammatory reactions.We have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish differentially expressed genes induced by TPA stimulation between the P2ry6+/+ and P2ry6-/- mice. Notably, P2ry6 deletion prevented the TPA-induced increase in YAP nuclear accumulation and hence its downstream gene expression in an MST/LATS1-dependent manner.
Project description:Comparison of mouse macrophage responses to lipopolysaccharide (LPS) and 12-o-tetradecanoylphorbol-13-acetate (TPA) between wild-type and NcoR-/- mice.