고명곤 교수

The Ten-Eleven-Translocation 2 (TET2) gene encodes a member of TET family enzymes that alters the epigenetic status of DNA by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies, including myelodysplastic syndromes, myeloproliferative neoplasms, and chronic myelomonocytic leukemia. By analyzing mice with targeted disruption of the Tet2 catalytic domain, we show here that Tet

TET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumour suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. Here we show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukaemia in mice, pointing to a causative role for TET loss-of-function in this myeloid malignancy. Phenotypic and trans

DNA methylation has pivotal regulatory roles in mammalian development, retrotransposon silencing, genomic imprinting, and X-chromosome inactivation. Cancer cells display highly dysregulated DNA methylation profiles characterized by global hypomethylation in conjunction with hypermethylation of promoter CpG islands that presumably lead to genome instability and aberrant expression of tumor suppressor genes or oncogenes. The recent discovery of ten-eleven-translocation (TET) family dioxygenases th

The methylation of cytosine and subsequent oxidation constitutes a fundamental epigenetic modification in mammalian genomes, and its abnormalities are intimately coupled to various pathogenic processes including cancer development. Enzymes of the Ten-eleven translocation (TET) family catalyze the stepwise oxidation of 5-methylcytosine in DNA to 5-hydroxymethylcytosine and further oxidation products. These oxidized 5-methylcytosine derivatives represent intermediates in the reversal of cytosine m

During the process of B cell development, transcription factors, such as E2A and Ebf1, have been known to play key roles. Although transcription factors and chromatin regulators work in concert to direct the expression of B lineage-specific genes, little is known about the involvement of regulators for chromatin structure during B lymphopoiesis. In this article, we show that deletion of Srg3/mBaf155, a scaffold subunit of the SWI/SNF-like BAF complex, in the hematopoietic lineage caused defects

The TET-family enzymes TET1, TET2, and TET3 influence DNA methylation by modifying 5-methylcytosine. Somatic loss-of-function mutations in TET2 are frequently observed in myeloid neoplasms. In this issue of Blood, Li et al. demonstrate that ablation of Tet2 alters the homeostasis and function of hematopoietic stem cells (HSCs) and induces leukemia in mice, as also reported by other groups.

Ten-eleven-translocation (TET) proteins modify DNA methylation by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Loss of 5hmC, a widely accepted epigenetic hallmark of cancers, is proposed as a biomarker for early cancer diagnosis and prognosis. Thus, precise quantification of 5hmC holds great potential for diverse clinical applications. DNAs containing 5mC or 5hmC display different adsorption affinity toward the gold surface, thus producing different electrochemical respons

β-adrenergic receptor (β-AR) signaling plays predominant roles in modulating energy expenditure by triggering lipolysis and thermogenesis in adipose tissue, thereby conferring obesity resistance. Obesity is associated with diminished β3-adrenergic receptor (β3-AR) expression and decreased β-adrenergic responses, but the molecular mechanism coupling nutrient overload to catecholamine resistance remains poorly defined. Ten-eleven translocation (TET) proteins are dioxygenases that alter the methyla

Activation of T cell antigen receptor (TCR) signaling inhibits glucocorticoid (GC)-induced apoptosis of T cells. However, the detailed mechanism regarding how activated T cells are protected from GC-induced apoptosis is unclear. Previously, we have shown that the expression level of SRG3, a murine homolog of BAF155 in humans, correlated well with the GC sensitivity of T cells either in vitro or in vivo. Intriguingly, the expression of SRG3 decreased upon positive selection in the thymus. Here we