ArticleCell death & disease2012
Grainyhead-like 2 (GRHL2) inhibits keratinocyte differentiation through epigenetic mechanism.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
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- Massively parallel analysis of genotype-dependent enhancer activity among atopic dermatitis genetic risk variants.The Journal of allergy and clinical immunology · 2025Article
- Alternate Grainy head isoforms regulate Drosophila midgut intestinal stem cell differentiation.Cell death discovery · 2025Article
- Crotonylation deficiency of S100A7 K49 promotes psoriatic keratinocyte proliferation through enhanced interaction with RAGE.Scientific reports · 2025Article
- Histone Modifications and DNA Methylation in Psoriasis: A Cellular Perspective.Clinical reviews in allergy & immunology · 2025Review
- GRHL2 regulates keratinocyte EMT-MET dynamics and scar formation during cutaneous wound healing.Cell death & disease · 2024Article
- The Impact of Disease Severity on the Serum Levels of Significant Neutrophil Extracellular Trap (NET) Proteins in Patients with Psoriasis.International journal of molecular sciences · 2024Article
- Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases.Journal of pharmaceutical analysis · 2024Review
- Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample.Cell · 2024Article
- Comparative Analysis of Olive-Derived Phenolic Compounds' Pro-Melanogenesis Effects on B16F10 Cells and Epidermal Human Melanocytes.International journal of molecular sciences · 2024Article
- Direct Lineage Reprogramming for Induced Keratinocyte Stem Cells: A Potential Approach for Skin Repair.Stem cells translational medicine · 2023Review
- Liquid biopsy: an examination of platelet RNA obtained from head and neck squamous cell carcinoma patients for predictive molecular tumor markers.Exploration of targeted anti-tumor therapy · 2023Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- Role of Histone Post-Translational Modifications in Inflammatory Diseases.Frontiers in immunology · 2022Review
- Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep.BMC biology · 2021Article
- Transcription factors Krüppel-like factor 4 and paired box 5 regulate the expression of the Grainyhead-like genes.PloS one · 2021Article
- CircZDHHC20 represses the proliferation, migration and invasion in trophoblast cells by miR-144/GRHL2 axis.Cancer cell international · 2020Article
- 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
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
We recently identified Grainyhead-like 2 (GRHL2), a mammalian homolog of Grainyhead in Drosophila, to be a novel transcription factor that regulates hTERT gene expression and enhances proliferation of normal human epidermal keratinocytes (NHEK). In the current study, we show that GRHL2 impairs keratinocyte differentiation through transcriptional inhibition of the genes clustered at the epidermal differentiation complex (EDC), located at chromosome 1q21. Gene expression profiling and subsequent in vitro assays revealed consistent downregulation of EDC genes, for example, IVL, KRT1, FLG, LCEs, and SPRRs, in NHEK expressing exogenous GRHL2. In vivo binding assay by chromatin immunoprecipitation revealed GRHL2 association at the promoter regions of its target genes, many of which belong to EDC. Exogenous GRHL2 expression also inhibited recruitment of histone demethylase Jmjd3 to the EDC gene promoters and enhanced the level of histone 3 Lys 27 trimethylation enrichment at these promoters. Survey of GRHL2 expression in human skin tissues demonstrated enhanced protein and mRNA levels in chronic skin lesions with impaired keratinocyte differentiation, for example, atopic dermatitis and psoriasis, compared with normal epidermis. These data indicate that GRHL2 impairs epidermal differentiation by inhibiting EDC gene expression through epigenetic mechanisms and support its role in the hyperproliferative skin diseases.
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Registered trials
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.