TIN2 deficiency leads to ALT-associated phenotypes and differentiation defects in embryonic stem cells.

ABSTRACT: Telomere integrity is critical for embryonic development, and core telomere-binding proteins, such as TIN2, are key to maintaining telomere stability. Here, we report that homozygous Tin2^S341X resulted in embryonic lethality in mice and reduced expression of Tin2 in the derived mouse embryonic stem cells (mESCs). Homozygous mutant mESCs were able to self-renew and remain undifferentiated but displayed many phenotypes associated with alternative lengthening of telomeres (ALT), including excessively long and heterogeneous telomeres, increased ALT-associated promyelocytic leukemia (PML) bodies, and unstable chromosomal ends. These cells also showed upregulation of Zscan4 expression and elevated targeting of DAXX/ATRX and H3K9me3 marks on telomeres. Furthermore, the mutant mESCs wer

SUBMITTER: Yin S 

PROVIDER: S-EPMC9120858 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature