ArticleNature communications2021
The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- KMT2D temporally activates neuronal transcriptional factor genes to mediate cerebellar granule cell differentiation.Science advances · 2025Article
- MLL4 regulates postnatal palate growth and midpalatal suture development.Frontiers in cell and developmental biology · 2025Article
- Mll4 in skeletal muscle fibers maintains muscle stem cells.Skeletal muscle · 2024Article
- MLL4 regulates postnatal palate growth and midpalatal suture development.bioRxiv : the preprint server for biology · 2024Article
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
- Five years of experience in the Epigenetics and Chromatin Clinic: what have we learned and where do we go from here?Human genetics · 2024Article
- Knockdown of Kmt2d leads to growth impairment by activating the Akt/β-catenin signaling pathway.G3 (Bethesda, Md.) · 2024Article
- The Hypothalamic Epigenetic Landscape in Dietary Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Molecular mechanism of specific DNA sequence recognition by NRF1.Nucleic acids research · 2024Article
- Transcriptional and epigenetic dysregulation impairs generation of proliferative neural stem and progenitor cells during brain aging.Nature aging · 2024Article
- Molecular insights of KMT2D and clinical aspects of Kabuki syndrome type 1.Birth defects research · 2023Review
- Rare diseases of epigenetic origin: Challenges and opportunities.Frontiers in genetics · 2023Review
- Ontogenetic rules for the molecular diversification of hypothalamic neurons.Nature reviews. Neuroscience · 2022Review
- Selective requirement for polycomb repressor complex 2 in the generation of specific hypothalamic neuronal subtypes.Development (Cambridge, England) · 2022Article
- Nonhistone Lysine Methylation as a Protein Degradation Signal.Journal of chemistry · 2022Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
In humans, inactivating mutations in MLL4, which encodes a histone H3-lysine 4-methyltransferase, lead to Kabuki syndrome (KS). While dwarfism is a cardinal feature of KS, the underlying etiology remains unclear. Here we report that Mll4 regulates the development of growth hormone-releasing hormone (GHRH)-producing neurons in the mouse hypothalamus. Our two Mll4 mutant mouse models exhibit dwarfism phenotype and impairment of the developmental programs for GHRH-neurons. Our ChIP-seq analysis reveals that, in the developing mouse hypothalamus, Mll4 interacts with the transcription factor Nrf1 to trigger the expression of GHRH-neuronal genes. Interestingly, the deficiency of Mll4 results in a marked reduction of histone marks of active transcription, while treatment with the histone deacetylase inhibitor AR-42 rescues the histone mark signature and restores GHRH-neuronal production in Mll4 mutant mice. Our results suggest that the developmental dysregulation of Mll4-directed epigenetic control of transcription plays a role in the development of GHRH-neurons and dwarfism phenotype in mice.
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