ArticleHuman molecular genetics2018
Building a schizophrenia genetic network: transcription factor 4 regulates genes involved in neuronal development and schizophrenia risk.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Clinical, cellular, and genomic consequences of a population-enrichedResearch square · 2026Article
- Identification and prioritization of gene sets associated with schizophrenia risk by network analysis.Psychopharmacology · 2026Article
- Repeated Clozapine Administration Causes Extensive Changes to the Expression of Coding and Non-coding RNAs, Including miR-124, in the Mouse Frontal Cortex.Molecular neurobiology · 2025Article
- Transcription factor 4 regulates the interhemispheric midline remodeling through neuron-astroglia communications during corpus callosum formation.Translational psychiatry · 2025Article
- A novel human organoid model system reveals requirement of TCF4 for oligodendroglial differentiation.Life science alliance · 2025Article
- An attempt to explain what intrinsically disordered TCF4 does in its spare time when PTHS-related mutations prevent it from doing its job.Cell communication and signaling : CCS · 2025Review
- Genetically regulated eRNA expression predicts chromatin contact frequency and reveals genetic mechanisms at GWAS loci.Nature communications · 2025Article
- Recruitment of homodimeric proneural factors by conserved CAT-CAT E-boxes drives major epigenetic reconfiguration in cortical neurogenesis.Nucleic acids research · 2024Article
- TCF4 Mutations Disrupt Synaptic Function Through Dysregulation of RIMBP2 in Patient-Derived Cortical Neurons.Biological psychiatry · 2024Article
- Psychiatric risk gene Transcription Factor 4 (TCF4) regulates the density and connectivity of distinct inhibitory interneuron subtypes.Molecular psychiatry · 2023Article
- Evaluating Gene Expression and Methylation Profiles of TCF4, MBP, and EGR1 in Peripheral Blood of Drug-Free Patients with Schizophrenia: Correlations with Psychopathology, Intelligence, and Cognitive Impairment.Journal of molecular neuroscience : MN · 2023Article
- TCF4 mutations disrupt synaptic function through dysregulation of RIMBP2 in patient-derived cortical neurons.bioRxiv : the preprint server for biology · 2023Article
- Psychiatric risk gene transcription factor 4 preferentially regulates cortical interneuron neurogenesis during early brain development.Journal of biomedical research · 2022Article
- Article
- miR-155-5p in the spinal cord regulates hypersensitivity in a rat model of bone cancer pain.Molecular pain · 2022Article
- Integrative omics of schizophrenia: from genetic determinants to clinical classification and risk prediction.Molecular psychiatry · 2022Review
- Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features.Genes · 2021Article
- Combined cellomics and proteomics analysis reveals shared neuronal morphology and molecular pathway phenotypes for multiple schizophrenia risk genes.Molecular psychiatry · 2021Article
- TCF4-mediated Fuchs endothelial corneal dystrophy: Insights into a common trinucleotide repeat-associated disease.Progress in retinal and eye research · 2021Review
- Molecular and Cellular Function of Transcription Factor 4 in Pitt-Hopkins Syndrome.Developmental neuroscience · 2021Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcription factor 4 (TCF4) locus is a robust association finding with schizophrenia (SCZ), but little is known about the genes regulated by the encoded transcription factor. Therefore, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) of TCF4 in neural-derived (SH-SY5Y) cells to identify genome-wide TCF4 binding sites, followed by data integration with SCZ association findings. We identified 11 322 TCF4 binding sites overlapping in two ChIP-seq experiments. These sites are significantly enriched for the TCF4 Ebox binding motif (>85% having ≥1 Ebox) and implicate a gene set enriched for genes downregulated in TCF4 small-interfering RNA (siRNA) knockdown experiments, indicating the validity of our findings. The TCF4 gene set was also enriched among (1) gene ontology categories such as axon/neuronal development, (2) genes preferentially expressed in brain, in particular pyramidal neurons of the somatosensory cortex and (3) genes downregulated in postmortem brain tissue from SCZ patients (odds ratio, OR = 2.8, permutation P < 4x10-5). Considering genomic alignments, TCF4 binding sites significantly overlapped those for neural DNA-binding proteins such as FOXP2 and the SCZ-associated EP300. TCF4 binding sites were modestly enriched among SCZ risk loci from the Psychiatric Genomic Consortium (OR = 1.56, P = 0.03). In total, 130 TCF4 binding sites occurred in 39 of the 108 regions published in 2014. Thirteen genes within the 108 loci had both a TCF4 binding site ±10kb and were differentially expressed in siRNA knockdown experiments of TCF4, suggesting direct TCF4 regulation. These findings confirm TCF4 as an important regulator of neural genes and point toward functional interactions with potential relevance for SCZ.
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