Project description:H3K36 methylation plays an important role in gene regulation. The role of H3K36 demethylase Kdm2b has been well studied. However, the role of Kdm2a in embryonic stem cells are still unkonwn. To study the function of Kdm2a in embryonic stem cells. We used CRISPR-gRNA system to knockout Kdm2a. We analyzed the gene expression change and identified target genes and repeats of Kdm2a. We uncovered a novel role of Kdm2a in regulating gene expression in embryonic stem cells.
Project description:Eukaryotic gene expression profiles are largely defined by transcription factors that recognize specific DNA sequences in gene regulatory regions and impact RNA polymerase recruitment and transcription. In addition to specific core promoter regulatory elements, up to 70% of genes in higher eukaryotes are also characterized by an overrepresentation of cytosine/guanine base pairs (CpGs) surrounding promoters and gene regulatory units. These features, called CpG islands, were identified over twenty years ago but there remains little mechanistic evidence to suggest how these enigmatic elements contribute to promoter function, with the exception that they are refractory to epigenetic silencing by DNA methylation. Here we uncover a role for CpG islands in buffering gene regulatory elements from repressive histone H3 lysine 36 methylation by directly recruiting the H3K36 specific lysine demethylase enzyme KDM2A. KDM2A is recruited to CpG islands by a zinc finger CxxC (ZF-CxxC) domain that specifically recognizes CpG DNA and is blocked by DNA methylation. This capacity to sense the epigenetic methylation state of DNA constrains KDM2A to non-methylated CpG islands. Importantly, these observations suggest CpG islands may function to delineate gene regulatory elements from bulk chromatin by recruiting factors that create unique chromatin architecture. This study provides information about binding of lysine demethylase enzyme KDM2A in mouse embryonic stem cells.
Project description:KDM2A is a histone demethylase, which primarily catalyzes the demethylation of H3K36me2. Abnormal expression of KDM2A is observed in many types of cancers; however, the molecular events connected to KDM2A expression remain unclear. In this work, to gain further insight into the molecular mechanism underlying the function of KDM2A, we analyzed the expression and function of KDM2A in esophageal squamous cell carcinoma (ESCC) cells.
