Regulation and function of telomerase in T cells

National Institute On Aging

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Abstract

Telomerase activity is tightly regulated during T cell development, differentiation, and activation. In peripheral blood resting T cells, telomerase activity is low to undetectable despite both telomerase components (TERT and TER) are expressed. To understand the transcriptional regulation of telomerase, we focused on TERT gene and analyzed the chromatin state of TERT in resting and activated T cells. We found that the amounts of histone methylation (H3K4me3) and acetylation (H3K9ac) in the promoter of TERT gene were quite low in resting T cells but increased after in vitro stimulation. This change is in parallel with the increase of mRNA amount of TERT. Furthermore, analysis of the mRNA of TERT showed the full-length transcripts as well as different alternative splicing products in activated T cells, to a much less degree in resting T cells. As the alternative splicing products of TERT resulted from frame shift or termination, they are presence indicating a mechanism that regulates telomerase at the post-transcriptional level. Currently, we are determining the relationship of alternative splicing products of TERT and T cell activation states and fate.