From this integrated analysis, we provide a comprehensive and annotated catalog of all currently known <i>CTCF</i> mutations associated with NDD phenotypes, to aid diagnostic applications, as well as translational and basic research.
We significantly broaden the mutational and clinical spectrum ofCTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.
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 clinic …
Here we used a series of CTCF mutations to explore CTCF’s relationship with chromatin and its contribution to gene regulation. CTCF’s impact depends on the genomic context of bound sites and the unique binding properties of WT and mutant CTCF ...
By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo missense mutation in CTCF in individuals with intellectual disability, microcephaly, and growth retardation. Furthermore, an individual with a larger deletion including CTCF was identified.
The disorder is caused by heterozygous, pathogenic variants (larger deletions, truncating variants or missense variants within the zinc-finger domains) in the CTCF -gene on chromosome 16q22.1, which encodes for an important chromatin organizer.
Here we used a series of CTCF mutations to explore CTCF’s relationship with chromatin and its contribution to gene regulation. CTCF’s impact depends o…
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 explored the regulatory roles of a clinically relevant R567W point mutation, located within the 11th zinc finger of CTCF, by introducing ...
CTCF and REST characterize distinctive clusters of genomic regions that increase or slowly decrease chromatin accessibility, respectively, in response to SWI/SNF inhibitors in mESCs. 18 We now demonstrate that both CTCF- and REST-enriched clusters are associated with PBAF regions with unique responses to SWI/SNF inhibition.
We now report on 39 additional individuals with variants in CTCF, further delineating the mutational and clinical spectrum of CTCF -related neurodevelopmental disorders (NDD). By RNA-sequencing we confirm a broad deregulation of genes in five affected individuals.
The predicted impact of the mutations in ZFs of CTCF on its 3D protein structure and the inferred possible effects on CTCF binding to chromatin. Mutations of CTCF coding sequence in cancer and their functional role in oncogenesis
Here we used a series of CTCF mutations to explore CTCF's relationship with chromatin and its contribution to gene regulation. CTCF's impact depends on the genomic context of bound sites and the unique binding properties of WT and mutant CTCF proteins. Specifically, CTCF's signal strength is linked …
CTCF and cohesin were found highly enriched in both common and haplotype-specific borders, whereas housekeeping genes and chromatin accessibility (ATAC-seq) are more strongly enriched in common borders (Fig. EV2E).
CTCF is also a tumour suppressor frequently mutated in cancer, however, the structural and functional impact of mutations have not been examined. We performed molecular and structural characterisation of five cancer-specific CTCF missense zinc finger (ZF) mutations occurring within key intra- and inter-ZF residues.
However, common effects of truncating mutations and deletions of CTCF on cell proliferation reveal CTCF as a critical regulator of normal cell and organ homeostasis.
