ArticleThe Journal of biological chemistry2012
The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 89 citations in OpenAlex.
- GRHL2 contributes to the maintenance of intestinal epithelial barrier integrity during LPS-induced injury.Frontiers in immunology · 2026Article
- Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential.Communications biology · 2025Article
- Fibroblast Growth Factors in Lung Development and Regeneration: Mechanisms and Therapeutic Potential.Cells · 2025Review
- Hepatocyte differentiation requires anisotropic expansion of bile canaliculi.Development (Cambridge, England) · 2024Article
- E74‑like ETS transcription factor 5 facilitates cell proliferation through regulating the expression of adenomatous polyposis coli 2 in non‑small cell lung cancer.International journal of molecular medicine · 2023Article
- GRHL2-controlled gene expression networks in luminal breast cancer.Cell communication and signaling : CCS · 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
- Single-cell gene regulation network inference by large-scale data integration.Nucleic acids research · 2022Article
- FoxA1 and FoxA2 control growth and cellular identity in NKX2-1-positive lung adenocarcinoma.Developmental cell · 2022Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- KLF4 Induces Mesenchymal-Epithelial Transition (MET) by Suppressing Multiple EMT-Inducing Transcription Factors.Cancers · 2021Article
- Grhl3 promotes retention of epidermal cells under endocytic stress to maintain epidermal architecture in zebrafish.PLoS genetics · 2021Article
- Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT.Oncotarget · 2020Article
- Functional roles of Grainyhead-like transcription factors in renal development and disease.Pediatric nephrology (Berlin, Germany) · 2020Review
- Spotlight on the Granules (Grainyhead-Like Proteins) - From an Evolutionary Conserved Controller of Epithelial Trait to Pioneering the Chromatin Landscape.Frontiers in molecular biosciences · 2020Review
- GRHL2 Acts as an Anti-Oncogene in Bladder Cancer by Regulating ZEB1 in Epithelial-Mesenchymal Transition (EMT) Process.OncoTargets and therapy · 2020Article
- Grainyhead-like 2 as a double-edged sword in development and cancer.American journal of translational research · 2020Review
- The Transcription FactorCells · 2019Article
- Human Papillomavirus 16 E6 Induces FoxM1B in Oral Keratinocytes through GRHL2.Journal of dental research · 2018Article
- The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes.Nature genetics · 2018Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The Grainyhead family of transcription factors controls morphogenesis and differentiation of epithelial cell layers in multicellular organisms by regulating cell junction- and proliferation-related genes. Grainyhead-like 2 (Grhl2) is expressed in developing mouse lung epithelium and is required for normal lung organogenesis. The specific epithelial cells expressing Grhl2 and the genes regulated by Grhl2 in normal lungs are mostly unknown. In these studies we identified the NK2-homeobox 1 transcription factor (Nkx2-1) as a direct transcriptional target of Grhl2. By binding and transcriptional assays and by confocal microscopy we showed that these two transcription factors form a positive feedback loop in vivo and in cell lines and are co-expressed in lung bronchiolar and alveolar type II cells. The morphological changes observed in flattening lung alveolar type II cells in culture are associated with down-regulation of Grhl2 and Nkx2-1. Reduction of Grhl2 in lung epithelial cell lines results in lower expression levels of Nkx2-1 and of known Grhl2 target genes. By microarray analysis we identified that in addition to Cadherin1 and Claudin4, Grhl2 regulates other cell interaction genes such as semaphorins and their receptors, which also play a functional role in developing lung epithelium. Impaired collective cell migration observed in Grhl2 knockdown cell monolayers is associated with reduced expression of these genes and may contribute to the altered epithelial phenotype reported in Grhl2 mutant mice. Thus, Grhl2 functions at the nexus of a novel regulatory network, connecting lung epithelial cell identity, migration, and cell-cell interactions.
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