Project description:To investigate the DNA binding sites associated with HES1, a CUT & Tag assay was conducted utilizing an anti-flag antibody to isolate the DNA sequences that interact with HES1. Subsequently, these DNA sequences were subjected to analysis through DNA-seq. The results indicated that HES1 has the capability to bind to the promotor-transcription start sites of 1140 genes.
Project description:Notch signaling modulates skeletal formation and osteoarthritis (OA) development through induction of catabolic factors. Here we examined functional roles of Hes1, the representative downstream transcription factor of Notch signaling, during these processes. Chromatin immunoprecipitation-sequencing (ChIP-seq) identified resposive elements of Hes1 around gene loci of Mmp13 and Adamts5, which were catabolic enzymes of cartilage matrix. Examination of HES1 binding site in human chondrogenic SW1353 cells.
Project description:Notch signaling modulates skeletal formation and osteoarthritis (OA) development through induction of catabolic factors. Here we examined functional roles of Hes1, the representative downstream transcription factor of Notch signaling, during these processes. Chromatin immunoprecipitation-sequencing (ChIP-seq) identified resposive elements of Hes1 around gene loci of Mmp13 and Adamts5, which were catabolic enzymes of cartilage matrix.
Project description:To investigate target molecules of HES1, we transduced GFP or HES1 into mouse chondrocyte cell line ATDC5, and performed the microarray analysis. HES1 overexpression increased inflammation-related genes including Il6 and Il1rl1.
Project description:To investigate the role of HES1 during glucocorticoid signaling in the liver, we employed whole-genome microarray expressions in liver mRNA extracted from control and Hes1-liver knockout male mice (HESKOL) that had been adrenalectomized to remove endogenous glucocorticoids.
Project description:High levels of Hes1 expression are frequently found in BCR-ABL-positive chronic myelogenous leukemia in blast crisis (CML-BC). In mouse bone marrow transplantation (BMT) models, co-expression of BCR-ABL and Hes1 induces CML-BC–like disease; however the underlying mechanism remained elusive. Here, based on gene expression analysis, we show that MMP-9 is upregulated by Hes1 in common myeloid progenitors (CMPs). Analysis of promoter activity demonstrated that Hes1 upregulated MMP-9 by activating NF-kB. Analysis of 20 samples from CML-BC patients showed that MMP-9 was highly expressed in three, with two exhibiting high levels of Hes1 expression. Interestingly, MMP-9 deficiency impaired the cobblestone area-forming ability of CMPs expressing BCR-ABL and Hes1 that were in conjunction with a stromal cell layer. In addition, these CMPs secreted MMP-9, promoting the release of soluble Kit-ligand (sKitL) from stromal cells, thereby enhancing proliferation of the leukemic cells. In accordance, mice transplanted with CMPs expressing BCR-ABL and Hes1 exhibited high levels of sKitL as well as MMP-9 in the serum. Importantly, MMP-9 deficiency impaired the development of CML-BC–like disease induced by BCR-ABL and Hes1 in mouse BMT models. The present results suggest that Hes1 promotes the development of CML-BC, partly through MMP-9 upregulation in leukemic cells.
Project description:We sequenced DNA isolated from performing ChIP of full-length KLF6 and an Input sample in an HCC cell line. The goal is to determine KLF6 binding sites in a mouse-derived HCC cell line. Determination of KLF6 binding sites in an HCC cell line using 2 control input libraries and 2 KLF6-ChIP libraries