Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage ...
Mutations of CTCF coding sequence in cancer and their functional role in oncogenesis. The DNA sequence encoding CTCF was first shown to be affected in breast and prostate tumours (Filippova et al, 1998). The analysis of several large Pan Cancer data sets including the TCGA data revealed a whole spectrum of CTCF mutations including deletions ...
Introduction. Mutations in CTCF (CCCTC-binding factor; MIM 604167) were first reported by Gregor et al 1 in individuals with intellectual disability of varying severity, microcephaly and growth retardation. The CTCF gene is located at 16q22.1, and encodes a transcriptional regulator with 11 highly conserved zinc finger domains that bind different DNA target sequences and proteins, with ...
Introduction: CTCF-related disorder (CRD) is a neurodevelopmental disorder (NDD) caused by monoallelic pathogenic variants in CTCF.The first CTCF variants in CRD cases were documented in 2013. To date, 76 CTCF variants have been further described in the literature. In recent years, due to the increased application of next-generation sequencing (NGS), growing numbers of CTCF variants are being ...
Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. ... Kouwenhoven EN, et al. De novo mutations in the genome organizer 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. CTCF (CCCTC-binding factor ...
CTCF mutations also affect the trajectory of exit from pluripotency. Indeed, while both WT and CTCF mutant cells tend to acquire a neuroectodermal expression profile upon LIF withdrawal, we observed mutant-specific transcriptional signatures of other germ layers, suggesting a more heterogeneous differentiation trajectory, which could be ...
Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased applicatio …
Rare Single Gene Mutation, Syndromic, Functional Relevance to Autism Two de novo loss-of-function variants and several de novo missense variants in the CTCF gene have been identified in ASD probands from the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort (Iossifov et al., 2014; Krumm et al., 2015; Zhou et al., 2022).
An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. 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 ...
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 ...
INTRODUCTION. CCCTC-binding factor CTCF is one of the most important chromatin organizers in vertebrates. It is crucial for orchestrating the three-dimensional chromatin structure by intra- and interchromosomal loop formation and by contributing to the organization of topologically associated domains. 1,2 Additionally, it is involved in many chromatin regulating processes, including gene ...
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 …
Cancer-associated CTCF mutations include stop codon mutations that are found distributed throughout its three regions (N-Terminal, C-Terminal, ZFs) . Depending on the location, the stop codon may not necessarily lead to loss of binding, but it could have a dominant negative impact due to its inability to bind co-factors that mediate its ...
For instance, mutations in enhancer elements that affect their looping interactions with target gene promoters have been linked to developmental disorders. ... (CTCF), a highly conserved zinc-finger DNA-binding protein. CTCF recognizes and binds to specific DNA sequences, with a consensus motif typically represented as 5′-CCACNAGGTGGCAG-3 ...
