KDM3A-mediated demethylation of histone H3 lysine 9 facilitates the chromatin binding of Neurog2 during neurogenesis

Hao Lin, Xuechen Zhu, Geng Chen, Lei Song, Li Gao, Aftab A. Khand, Ying Chen, Gufa Lin, Qinghua Tao

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Neurog2 is a crucial regulator of neuronal fate specification and differentiation in vivo and in vitro. However, it remains unclear how Neurog2 transactivates neuronal genes that are silenced by repressive chromatin. Here, we provide evidence that the histone H3 lysine 9 demethylase KDM3A facilitates the Xenopus Neurog2 (formerly known as Xngnr1) chromatin accessibility during neuronal transcription. Loss-of-function analyses reveal that KDM3A is not required for the transition of naive ectoderm to neural progenitor cells but is essential for primary neuron formation. ChIP series followed by qPCR analyses reveal that Neurog2 promotes the removal of the repressive H3K9me2 marks and addition of active histone marks, including H3K27ac and H3K4me3, at the NeuroD1 and Tubb2b promoters; this activity depends on the presence of KDM3A because Neurog2, via its C-terminal domain, interacts with KDM3A. Interestingly, KDM3A is dispensable for the neuronal transcription initiated by Ascl1, a proneural factor related to neurogenin in the bHLH family. In summary, our findings uncover a crucial role for histone H3K9 demethylation during Neurog2-mediated neuronal transcription and help in the understanding of the different activities of Neurog2 and Ascl1 in initiating neuronal development.

Original languageEnglish (US)
Pages (from-to)3674-3685
Number of pages12
JournalDevelopment (Cambridge)
Volume144
Issue number20
DOIs
StatePublished - Oct 15 2017

Keywords

  • Chromatin accessibility
  • H3K9me2
  • Histone demethylation
  • KDM3A
  • Neurog2
  • Neurogenesis

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    Lin, H., Zhu, X., Chen, G., Song, L., Gao, L., Khand, A. A., Chen, Y., Lin, G., & Tao, Q. (2017). KDM3A-mediated demethylation of histone H3 lysine 9 facilitates the chromatin binding of Neurog2 during neurogenesis. Development (Cambridge), 144(20), 3674-3685. https://doi.org/10.1242/dev.144113