Thomas R. Cech

Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization

Nature Reviews Molecular Cell Biology · 2021 · 269 citations

RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells

Nature Genetics · 2020 · 153 citations

The structure of human CST reveals a decameric assembly bound to telomeric DNA

Science · 2020 · 117 citations

The CTC1-STN1-TEN1 (CST) complex is essential for telomere maintenance and resolution of stalled replication forks genome-wide. Here, we report the 3.0-angstrom cryo-electron microscopy structure of human CST bound to telomeric single-stranded DNA (ssDNA), which assembles as a decameric supercomplex. The atomic model of the 134-kilodalton CTC1 subunit, built almost entirely de novo, reveals the overall architecture of CST and the DNA-binding anchor site. The carboxyl-terminal domain of STN1 inte…

Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation

Proceedings of the National Academy of Sciences · 2022 · 108 citations

Polycomb-group proteins play critical roles in gene silencing through the deposition of histone H3 lysine 27 trimethylation (H3K27me3) and chromatin compaction. This process is essential for embryonic stem cell (ESC) pluripotency, differentiation, and development. Polycomb repressive complex 2 (PRC2) can both read and write H3K27me3, enabling progressive spreading of H3K27me3 on the linear genome. Long-range Polycomb-associated DNA contacts have also been described, but their regulation and role…

Structural basis for inactivation of PRC2 by G-quadruplex RNA

Science · 2023 · 66 citations

Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding RNAs (lncRNAs) with a binding preference for G-quadruplex RNA. In this work, we present a 3.3-Å-resolution cryo-electron microscopy structure of PRC2 bound to a G-quadruplex RNA. Notably, RNA mediates the dimerization of PRC2 by binding both protomers and inducing a protein interface composed of two copies of the cataly…