Progerin impairs 3D genome organization and induces fragile telomeres by limiting the dNTP pools.

ABSTRACT: Chromatin organization within the nuclear volume is essential to regulate many aspects of its function and to safeguard its integrity. A key player in this spatial scattering of chromosomes is the nuclear envelope (NE). The NE tethers large chromatin domains through interaction with the nuclear lamina and other associated proteins. This organization is perturbed in cells from Hutchinson-Gilford progeria syndrome (HGPS), a genetic disorder characterized by premature aging features. Here, we show that HGPS-related lamina defects trigger an altered 3D telomere organization with increased contact sites between telomeres and the nuclear lamina, and an altered telomeric chromatin state. The genome-wide replication timing signature of these cells is perturbed, with a shift to earlier replication

SUBMITTER: Kychygina A 

PROVIDER: S-EPMC8222272 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature