The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus
- Authors
- Huisman, C.; Kim, Y.A.; Jeon, S.; Shin, B.; Choi, J.; Lim, S.J.; Youn, S.M.; Park, Y.; Medha, K.C.; Kim, S.; Lee, S.-K.; Lee, S.; Lee, J.W.
- Issue Date
- 11-Jan-2021
- Publisher
- Nature Research
- Citation
- Nature Communications, v.12, no.1
- Journal Title
- Nature Communications
- Volume
- 12
- Number
- 1
- URI
- http://scholarworks.bwise.kr/ssu/handle/2018.sw.ssu/40650
- DOI
- 10.1038/s41467-020-20511-7
- ISSN
- 2041-1723
- 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. © 2021, The Author(s).
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Collections - College of Natural Sciences > School of Systems and Biomedical Science > 1. Journal Articles
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