Role of telomeric repeat-containing RNA in telomeric chromatin remodeling during the early expansion of human embryonic stem cells

Abstract

This study aimed to explore the role of telomeric repeat-containing RNA (TERRA) in telomeric chromatin remodeling during the early expansion of human embryonic stem cells (hESCs). During the derivation of hESCs, histone demethylation in the telomeric region facilitates telomerase-mediated telomere elongation. An adequate telomere repeat is essential for hESCs to acquire and/or maintain the unlimited symmetric division, which suggests that there is a link between pluripotency and telomere maintenance. The present study found that the gradual decrease in TERRA levels and related TERRA foci were correlated with telomeric length elongation in the early expansion of hESCs. In addition, TERRA participated in telomeric chromatin remodeling by cooperating with SUV39H1 (suppressor of variegation 3-9 homolog 1/2) to propagate telomeric heterochromatin marker, histone H3 trimethylation of lysine 9. Moreover, the fibroblast growth factor signaling pathway, which is activated in hESCs, could suppress TERRA levels via telomeric repeat factor 1, which results in reduced SUV39H1 recruitment by TERRA at the telomere. Taken together, these results highlight the role of TERRA in hESC telomere elongation and homeostasis in the acquisition and/or maintenance of stem cell pluripotency.-Zeng, S., Liu, L., Sun, Y., Lu, G., Lin, G. Role of telomeric repeat-containing RNA in telomeric chromatin remodeling during the early expansion of human embryonic stem cells.

Keywords: TERRA; TRF1; histone demethylation; telomere length.