Cytosine Modifications and Distinct Functions of TET1 on Tumorigenesis

Abstract

Vast emerging evidences are linking the base modifications and gene expression involved in essential metabolic pathways. Among the base modification markers extensively studied, 5-methylcytosine (5mC) and its oxidative derivatives (5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC)) dynamically occur in DNA and RNA and have been acknowledged as the important epigenetic markers involved in regulation of cellular biological processes. The modification of C has been characterized biochemically, molecularly, and phenotypically, including elucidation of its methyltransferase complexes (writer), demethylases (eraser), 10-11 translocation proteins (TETs), and direct interaction proteins (readers). The levels and the landscapes of these epigenetic markers in the epitranscriptomes and epigenomes are precisely and dynamically regulated by the fine-tuned coordination of the writers and erasers in accordance with stages of the growth, development, and reproduction as naturally programmed during the life span. In mammalian genome, the TET family is consisted of three members, including TET1, TET2, and TET3. The link between aberrant modifications and diseases, such as cancers, neurodegenerative disorders, and heart diseases, has been appreciated. This review article will highlight the research advances in the writers and erasers for the modifications of cytosine in genome, as well as the dual function of TET1 in tumorigenesis as a tumor suppressor and a promoter. Additionally, the future research directions are addressed.

Expression of Ten-Eleven Translocation 1 Gene in Acute Leukemia

“…These ndings supported the role of TET1 in leukemogenesis. High TET1 expression in AML patients attributed to activation of cancer-speci c oncogenic mechanisms and correlated with the upregulation of RNA transport and ribosome biogenesis pathways initiating leukemia (19), ( 3), (20) .…”

“…These proposed pathogenic mechanisms are that the high TET1 expression correlates with the upregulation of RNA transport and ribosome biogenesis pathways driving tumorigenesis (3), (19) , whereas TET1 downregulation correlates with genetic and epigenetic changes in HSCs, which accumulate and predispose to develop leukemia (24) .…”

Expression of Ten-Eleven Translocation 1 Gene in Acute Leukemia

“…These ndings supported the role of TET1 in leukemogenesis. High TET1 expression in AML patients was attributed to activation of cancer-speci c oncogenic mechanisms and correlated with the upregulation of RNA transport and ribosome biogenesis pathways initiating leukemia (3,13,20).…”