ArticleNucleic acids research2018
Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Pioneer-factor activity requires stable chromatin occupancy mediated by both sequence-specific binding and disordered protein domains.Science advances · 2026Article
- Defining the DNA Binding Specificity of GRHL2.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic dissection of GRHL2 and PR transcriptional co-regulation in breast cells.PLoS genetics · 2026Article
- Transcriptomic Adjustment to Decreasing Oxygen Reveals Novel Functional Strategies for Extreme Hypoxia Tolerance in the Copepod Tigriopus californicus.Genome biology and evolution · 2026Article
- Article
- Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases.Histopathology · 2025Article
- Multi-omics integration uncovers key transcriptional regulators in triple-negative breast cancer spatial heterogeneity.Frontiers in genetics · 2025Article
- TFCP2 as a therapeutic nexus: unveiling molecular signatures in cancer.Cancer metastasis reviews · 2024Review
- Discovery of a non-canonical GRHL1 binding site using deep convolutional and recurrent neural networks.BMC genomics · 2023Article
- GRHL2 Regulation of Growth/Motility Balance in Luminal versus Basal Breast Cancer.International journal of molecular sciences · 2023Article
- Grainyhead-like 2 is required for morphological integrity of mouse embryonic stem cells and orderly formation of inner ear-like organoids.Frontiers in cell and developmental biology · 2023Article
- GRHL2 Enhances Phosphorylated Estrogen Receptor (ER) Chromatin Binding and Regulates ER-Mediated Transcriptional Activation and Repression.Molecular and cellular biology · 2022Article
- Article
- Structural and Functional Insights into CP2c Transcription Factor Complexes.International journal of molecular sciences · 2022Article
- The regulatory landscape of retinoblastoma: a pathway analysis perspective.Royal Society open science · 2022Article
- Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan.Nature communications · 2022Article
- Technologies for profiling the impact of genomic variants on transcription factor binding.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2021Article
- Single-cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics.Cell proliferation · 2021Article
- Transcriptional and Epigenetic Bioinformatic Analysis of Claudin-9 Regulation in Gastric Cancer.Journal of oncology · 2021Article
- Boar seminal plasma: current insights on its potential role for assisted reproductive technologies in swine.Animal reproduction · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Grainyhead (Grh)/CP2 transcription factors are highly conserved in multicellular organisms as key regulators of epithelial differentiation, organ development and skin barrier formation. In addition, they have been implicated as being tumor suppressors in a variety of human cancers. Despite their physiological importance, little is known about their structure and DNA binding mode. Here, we report the first structural study of mammalian Grh/CP2 factors. Crystal structures of the DNA-binding domains of grainyhead-like (Grhl) 1 and Grhl2 reveal a closely similar conformation with immunoglobulin-like core. Both share a common fold with the tumor suppressor p53, but differ in important structural features. The Grhl1 DNA-binding domain binds duplex DNA containing the consensus recognition element in a dimeric arrangement, supporting parsimonious target-sequence selection through two conserved arginine residues. We elucidate the molecular basis of a cancer-related mutation in Grhl1 involving one of these arginines, which completely abrogates DNA binding in biochemical assays and transcriptional activation of a reporter gene in a human cell line. Thus, our studies establish the structural basis of DNA target-site recognition by Grh transcription factors and reveal how tumor-associated mutations inactivate Grhl proteins. They may serve as points of departure for the structure-based development of Grh/CP2 inhibitors for therapeutic applications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.