ArticleHuman molecular genetics2020
Functions of Gtf2i and Gtf2ird1 in the developing brain: transcription, DNA binding and long-term behavioral consequences.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Separating direct, indirect, and parent-of-origin genetic effects in the human population.Cell genomics · 2026Article
- Modeling Williams syndrome from a neurodevelopmental perspective: recent advances, model-based translational insights and future directions.World journal of pediatrics : WJP · 2026Review
- The dietary ligands, omega-3 fatty acid endocannabinoids and short-chain fatty acids prevent cytokine-induced reduction of human hippocampal neurogenesis and alter the expression of genes involved in neuroinflammation and neuroplasticity.Molecular psychiatry · 2025Article
- Gtf2i-encoded transcription factor Tfii-i regulates myelination via Sox10 and Mbp regulatory elements.Nature communications · 2025Article
- Separating direct, indirect and parent-of-origin genetic effects in the human population.bioRxiv : the preprint server for biology · 2025Article
- Requirements for the neurodevelopmental disorder-associated gene ZNF292 in human cortical interneuron development and function.Cell reports · 2025Article
- Chromosomal and gonadal sex have differing effects on social motivation in mice.Biology of sex differences · 2025Article
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- Chromosomal and gonadal sex have differing effects on social motivation in mice.bioRxiv : the preprint server for biology · 2024Article
- Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors.Nature communications · 2024Article
- Novel CDKL5 targets identified in human iPSC-derived neurons.Cellular and molecular life sciences : CMLS · 2024Article
- Long-term isoflurane anesthesia induces cognitive deficits via AQP4 depolarization mediated blunted glymphatic inflammatory proteins clearance.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Characterization of early markers of disease in the mouse model of mucopolysaccharidosis IIIB.Journal of neurodevelopmental disorders · 2024Article
- Neuronal Gtf2i deletion alters mitochondrial and autophagic properties.Communications biology · 2023Article
- Extensive characterization of a Williams syndrome murine model shows Gtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior.Genes, brain, and behavior · 2023Article
- Biallelic GTF2IRD1 variants in brothers with profound neurodevelopmental disorder: A possible novel disorder involving a critical gene for Williams syndrome.American journal of medical genetics. Part A · 2023Article
- Extensive characterization of a Williams Syndrome murine model showsbioRxiv : the preprint server for biology · 2023Article
- Article
- Identification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis.Nature communications · 2021Article
- Core transcriptional networks in Williams syndrome: IGF1-PI3K-AKT-mTOR, MAPK and actin signaling at the synapse echo autism.Human molecular genetics · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
Gtf2ird1 and Gtf2i are two transcription factors (TFs) among the 28 genes deleted in Williams syndrome, and prior mouse models of each TF show behavioral phenotypes. Here we identify their genomic binding sites in the developing brain and test for additive effects of their mutation on transcription and behavior. GTF2IRD1 binding targets were enriched for transcriptional and chromatin regulators and mediators of ubiquitination. GTF2I targets were enriched for signal transduction proteins, including regulators of phosphorylation and WNT. Both TFs are highly enriched at promoters, strongly overlap CTCF binding and topological associating domain boundaries and moderately overlap each other, suggesting epistatic effects. Shared TF targets are enriched for reactive oxygen species-responsive genes, synaptic proteins and transcription regulators such as chromatin modifiers, including a significant number of highly constrained genes and known ASD genes. We next used single and double mutants to test whether mutating both TFs will modify transcriptional and behavioral phenotypes of single Gtf2ird1 mutants, though with the caveat that our Gtf2ird1 mutants, like others previously reported, do produce low levels of a truncated protein product. Despite little difference in DNA binding and transcriptome-wide expression, homozygous Gtf2ird1 mutation caused balance, marble burying and conditioned fear phenotypes. However, mutating Gtf2i in addition to Gtf2ird1 did not further modify transcriptomic or most behavioral phenotypes, suggesting Gtf2ird1 mutation alone was sufficient for the observed phenotypes.
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