The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex.
The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex.
复制标题
组蛋白脱甲基酶LSD1通过与PAX2和NURD阻遏物复合物的相互作用来调节内耳祖细胞分化。
DOI：
10.1371/journal.pone.0191689
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Hashino E
中科院分区：
文献类型：
--
作者：
Patel D;Shimomura A;Majumdar S;Holley MC;Hashino E
组蛋白去甲基化酶LSD 1在细胞分化中起关键作用，特别是在沉默谱系特异性基因中。然而，关于LSD 1如何调节内耳中的神经感觉分化知之甚少。在这里，我们表明，LSD 1直接与转录因子Pax 2相互作用，在小鼠耳神经元祖细胞系（VOT-N33）的Pax 2靶基因位点形成NuRD共阻遏复合物。表达Pax 2反应元件报告基因的VOT-N33细胞在未处理时为GFP阴性，但在强制分化或用有效的LSD抑制剂处理后变为GFP阳性。LSD 1活性的药理学抑制导致H3 K4的单甲基化和二甲基化的富集、感觉神经元基因的上调以及小鼠内耳类器官中感觉神经元数量的增加。总之，这些结果将LSD 1/NuRD复合物鉴定为以前未识别的Pax 2介导的内耳神经元分化的调节剂。
The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor. Pharmacological inhibition of LSD1 activity resulted in the enrichment of mono- and di-methylation of H3K4, upregulation of sensory neuronal genes and an increase in the number of sensory neurons in mouse inner ear organoids. Together, these results identify the LSD1/NuRD complex as a previously unrecognized modulator for Pax2-mediated neuronal differentiation in the inner ear.
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影响因子：
11.8
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
通讯作者：
Xu, Pin-Xian
DOI：
10.1073/pnas.0408239102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Kondo, T;Johnson, SA;Hashino, E
通讯作者：
Hashino, E
影响因子：
4
作者：
Kouzarides, T
通讯作者：
Kouzarides, T
DOI：
10.1073/pnas.93.24.13870
发表时间：
1996-11-26
影响因子：
11.1
作者：
Favor, J;Sandulache, R;Schughart, K
通讯作者：
Schughart, K
影响因子：
2.5
作者：
Lawoko-Kerali, G;Milo, M;Holley, MC
通讯作者：
Holley, MC