Fig. 6: A working model of ALT activation of mESCs. | Nature Communications

Fig. 6: A working model of ALT activation of mESCs.

From: Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells

Fig. 6

This figure summarises the emergence process of ALT mESC from various aspects. After the Terc gene was knocked out, cells of the early generation grew normally, but as the telomere length decreased growth slowed down and cells approached a senescent state. Affected by telomere shortening, genome-wide copy-number changes, and chromosomal fusions occurred, and transcriptional networks and cellular physiology changed accordingly. One or more cells activated ALT and were selected to form a homogenous post-ALT cell population. In an evolutionary time-line, the mTALT sequence was located at chromosome 13 first, and at a certain point, replicated at the end of chromosome 11. In the process of telomere shortening, the only mTALT of chromosome 11 underwent selective duplication, and during ALT activation, the mTALT of chromosome 11 was amplified in cis and trans to cover all telomeres. Through transcriptome and proteome analyses, we confirmed that genome-wide epigenetic remodelling occurred during the ALT activation process, and the expression of telomeric transcripts and R-loop formation increased due to HMGN1-dependent telomeric changes, contributing to telomere maintenance.

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