CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment.

ABSTRACT: The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explore the regulatory roles of a clinically relevant R567W point mutation, located within the 11^th zinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCF^R567W mutation exhibit growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single-cell transcriptome levels. This mutation induces premature stem-like cell exhaustion, accelera

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11217373 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature