Project description:FoxM1 is an oncogenic transcription factor that has been linked to the genesis and progression of cancer. FoxM1 not only upregulates cell proliferation and survival genes, but also represses tumor suppressor genes according to our prior study. This ChIP-Seq is a part of our endeveavor to creat a map of the FoxM1 occupied chromatin area in order to better understand the FoxM1 role in tumorigenesis. We present the results of a high-throughput profile of Chromatine alteration in mammalian cells using ChIP-Seq. We developed genome-wide chromatin-state maps of the human HCC cell line Huh7 by extracting approximately 3 billion bases of sequence from chromatin immunoprecipitated DNA in approxiamtoly 33 million reads. We discovered that FoxM1 successfully distinguishes between expressed, stably repressed and poised genes and therefore reflect cell state and lineage potential. This research lays the groundwork for using extensive chromatin profiling to characterize the genes controlled by the oncogeneic transcription factor FoxM1 and their role in the development of FoxM1-induced cancers.
Project description:FOXM1 is a key transcription factor regulating cell cycle progression, DNA damage response, and a host of other hallmark cancer features, but the role of the FOXM1 cistrome in driving estrogen receptor-positive (ER+) vs. ER- breast cancer clinical outcomes remains undefined. Chromatin immunoprecipitation sequencing (ChIP-Seq) coupled with RNA sequencing (RNA-Seq) analyses was used to identify FOXM1 target genes in breast cancer cells (MCF-7) where FOXM1 expression was either induced by cell proliferation or repressed by p53 upregulation.
Project description:We identified FOXM1 as an EAC-specific candidate transcription factor using GSEA analysis. Functionality of FOXM1 was evaluated in both EAC patient derived organoids and EAC cell lines by measuring cell proliferation, colony formation, and xenograft growth. A FOXM1 signature through the overlap of ESO26, SKGT4, and OE33 intersected ChIP-seq peaks and ESO26 siFOXM1 RNA-seq downregulated genes. Upstream transcriptional regulation of FOXM1 was evaluated with this FOXM1 gene signature and validated using pharmacological inhibition. GSEA analysis determined that immune related pathways were upregulated in ESO26 cell lines treated with siFOXM1 or in TCGA EAC patients with low FOXM1 expression. Syngeneic xenografts found increases in CD8+ T cell infiltration in FOXM1 knockdown tumors. Loss of FOXM1 led to increased secretion of CD8+ T cell Th1 chemokines which play a role in the migration of CD8+ T cells upon loss of FOXM1. Finally, the loss of FOXM1 also increased Ex-vivo cytotoxic killing of murine cancer cells.
Project description:We report the genome wide DNA binding patterns of wild type FOXM1 in asynchronous HeLa cells using chromatin precipitation followed by high-throughput sequencing (ChIP-seq). We find that FOXM1 is bound to the promoter of a number of cell cycle genes including PLK, AURKB, and CCNB1. FOXM1 ChIP-seq in asynchronous HeLa cells
Project description:FOXM1 is a key transcription factor regulating cell cycle progression, DNA damage response, and a host of other hallmark cancer features, but the role of the FOXM1 cistrome in driving estrogen receptor-positive (ER+) vs. ER- breast cancer clinical outcomes remains undefined. Chromatin immunoprecipitation sequencing (ChIP-Seq) coupled with RNA sequencing (RNA-Seq) analyses was used to identify FOXM1 target genes in breast cancer cells (MCF-7) where FOXM1 expression was either induced by cell proliferation or repressed by p53 upregulation.
Project description:MYBL2 is a transcription factor that has either pro-survival or anti-survival functions in a cell-type specific manner. Overexpression of MYBL2 is associated with worse survival of lung adenocarcinoma, but the mechanism by which it regulates transcription has not yet been elucidated. In this study, we found that MYBL2 mainly binds to the promoters of highly expressed genes in lung adenocarcinoma cells using ChIP-seq. Using knock-down and RNA-seq approach, we identified over a thousand of genes deregulated by MYBL2. By integrating ChIP-seq and RNA-seq data, we identified target genes of MYBL2. We revealed that FOXM1 is regulated by MYBL2 in lung adenocarcinoma cells, and FOXM1 binding sites are largely shared with MYBL2 binding sites. We treated lung adenocarcinoma cells with FDI-6, a known FOXM1 inhibitor and investigated the effect of FDI-6 in transcriptional regulation of MYBL2 and FOXM1. We found that CENPA is one of the key genes regulated by MYBL2 and FOXM1, and that it can be inhibited by FDI-6. Our signaling pathway analysis results revealed that MYBL2 and FOXM1 activate cell-cycle genes, suggesting that MYBL2 and FOXM1 act as oncogenic transcription factors in lung adenocarcinoma cells and FDI-6 could be a potential treatment of the disease.
