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ZMYND8 抑制 MAPT213 LncRNA 转录，促进神经元分化。

ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation.

机构信息

Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, 700064, India.

Structural Biology & Bio-Informatics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.

出版信息

Cell Death Dis. 2022 Sep 5;13(9):766. doi: 10.1038/s41419-022-05212-x.

DOI:10.1038/s41419-022-05212-x
PMID:36064715
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9445031/
Abstract

Zinc Finger transcription factors are crucial in modulating various cellular processes, including differentiation. Chromatin reader Zinc Finger MYND (Myeloid, Nervy, and DEAF-1) type containing 8 (ZMYND8), an All-Trans Retinoic Acid (ATRA)-responsive gene, was previously shown to play a crucial role in promoting the expression of neuronal-lineage committed genes. Here, we report that ZMYND8 promotes neuronal differentiation by positively regulating canonical MAPT protein-coding gene isoform, a key player in the axonal development of neurons. Additionally, ZMYND8 modulates gene-isoform switching by epigenetically silencing key regulatory regions within the MAPT gene, thereby suppressing the expression of non-protein-coding isoforms such as MAPT213. Genetic deletion of ZMYND8 led to an increase in the MAPT213 that potentially suppressed the parental MAPT protein-coding transcript expression related to neuronal differentiation programs. In addition, ectopic expression of MAPT213 led to repression of MAPT protein-coding transcript. Similarly, ZMYND8-driven transcription regulation was also observed in other neuronal differentiation-promoting genes. Collectively our results elucidate a novel mechanism of ZMYND8-dependent transcription regulation of different neuronal lineage committing genes, including MAPT, to promote neural differentiation.

摘要

锌指转录因子在调节各种细胞过程中至关重要，包括分化。先前已经表明，含 8 个锌指的 MYND（髓系、神经和 DEAF-1）型染色质读锌指（ZMYND8）是全反式视黄酸（ATRA）反应基因，在促进神经元谱系决定基因的表达中起着关键作用。在这里，我们报告 ZMYND8 通过正调控经典 MAPT 蛋白编码基因异构体来促进神经元分化，MAPT 是神经元轴突发育中的关键因子。此外，ZMYND8 通过表观遗传沉默 MAPT 基因内的关键调节区域来调节基因异构体的转换，从而抑制非蛋白编码异构体（如 MAPT213）的表达。ZMYND8 的遗传缺失导致 MAPT213 的增加，这可能抑制与神经元分化程序相关的亲本 MAPT 蛋白编码转录物的表达。此外，MAPT213 的异位表达导致 MAPT 蛋白编码转录物的抑制。同样，在其他促进神经元分化的基因中也观察到 ZMYND8 驱动的转录调节。总的来说，我们的结果阐明了 ZMYND8 依赖的转录调节不同神经元谱系决定基因（包括 MAPT）的新机制，以促进神经分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/572b098656f3/41419_2022_5212_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/5c2354407b4d/41419_2022_5212_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/22a79aa3536a/41419_2022_5212_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/d7ada1cb7ee2/41419_2022_5212_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/2a730d823b2f/41419_2022_5212_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/865d49193c5c/41419_2022_5212_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/ff76141f57bd/41419_2022_5212_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/db5b278b9b06/41419_2022_5212_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/572b098656f3/41419_2022_5212_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/5c2354407b4d/41419_2022_5212_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/22a79aa3536a/41419_2022_5212_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/d7ada1cb7ee2/41419_2022_5212_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/2a730d823b2f/41419_2022_5212_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/865d49193c5c/41419_2022_5212_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/ff76141f57bd/41419_2022_5212_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/db5b278b9b06/41419_2022_5212_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe46/9445031/572b098656f3/41419_2022_5212_Fig8_HTML.jpg

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本文引用的文献

1
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Front Immunol. 2021 Oct 11;12:738431. doi: 10.3389/fimmu.2021.738431. eCollection 2021.
2
Characterization of the Testis-specific Gene Reveals Isoform-specific Roles in Controlling Biological Processes.睾丸特异性基因的表征揭示了其在控制生物过程中的亚型特异性作用。
J Endocr Soc. 2021 Sep 27;5(11):bvab153. doi: 10.1210/jendso/bvab153. eCollection 2021 Nov 1.
3
Suppression of poised oncogenes by ZMYND8 promotes chemo-sensitization.
锌指同源盒4（ZFHX4）基因功能丧失是一种神经发育障碍的基础。
medRxiv. 2024 Aug 8:2024.08.07.24311381. doi: 10.1101/2024.08.07.24311381.
4
LINC MIR503HG Controls SC-β Cell Differentiation and Insulin Production by Targeting CDH1 and HES1.LINC MIR503HG 通过靶向 CDH1 和 HES1 控制胰岛 β 细胞分化和胰岛素生成。
Adv Sci (Weinh). 2024 Apr;11(13):e2305631. doi: 10.1002/advs.202305631. Epub 2024 Jan 20.
ZMYND8 抑制稳定的癌基因促进化疗敏感性。
Cell Death Dis. 2020 Dec 15;11(12):1073. doi: 10.1038/s41419-020-03129-x.
4
Diversity and Emerging Roles of Enhancer RNA in Regulation of Gene Expression and Cell Fate.增强子RNA在基因表达调控和细胞命运决定中的多样性及新作用
Front Cell Dev Biol. 2020 Jan 14;7:377. doi: 10.3389/fcell.2019.00377. eCollection 2019.
5
A novel role of tumor suppressor ZMYND8 in inducing differentiation of breast cancer cells through its dual-histone binding function.肿瘤抑制因子 ZMYND8 通过其双重组蛋白结合功能诱导乳腺癌细胞分化的新作用。
J Biosci. 2020;45.
6
High Positive Correlations between and -/-/- Gene Cluster Overexpression in Multi-Tumor Types Suggest Deregulated Activation of an Bidirectional Promoter.与多肿瘤类型中 -/-/- 基因簇过表达之间的高度正相关表明双向启动子的失调激活。
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7
Atypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor.UBR7 的非典型植物同源结构域作为 H2BK120Ub 连接酶和乳腺癌肿瘤抑制因子发挥作用。
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8
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9
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Cell Rep. 2018 Aug 21;24(8):2141-2154.e6. doi: 10.1016/j.celrep.2018.07.064.
10
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Trends Genet. 2018 Feb;34(2):142-157. doi: 10.1016/j.tig.2017.11.005. Epub 2018 Feb 7.