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XB-ART-54148
Development January 1, 2017; 144 (20): 3674-3685.

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

Lin H , Zhu X , Chen G , Song L , Gao L , Khand AA , Chen Y , Lin G , Tao Q .


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.

PubMed ID: 29042477
Article link: Development

Genes referenced: ascl1 dll1 ebf2 eef1a1 egr2 en2 fgf8 h3-3a hoxb9 isl1 kdm3a kdm4a krt12.5 mapk1 mnx1 msx1 myc myt1 neurod1 neurod4 neurog1 neurog2 nog pax6 rax smo snai1 sox1 sox2 sox3 sox9 tbxt tlx1 tubb2b ventx2.1 zic1
GO keywords: histone demethylation [+]
Antibodies: Acetylated H3f3 Ab37 H3f3 Ab30 H3f3 Ab35 H3f3 Ab36 Mapk1 Ab1 Mapk1 Ab10 Methyl-h3f3a Ab38 h3f3 Ab37 h3f3 Ab38 h3f3a Ab32 kdm3a Ab1 kdm4a Ab1 neurog2 Ab1
Morpholinos: ascl1 MO7 kdm3a MO1 kdm3a MO2 neurog2 MO2


Article Images: [+] show captions


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