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鼠 NuRD/Mi2 成分 P66α突变体是胚胎致死的。

Mutants in the mouse NuRD/Mi2 component P66alpha are embryonic lethal.

机构信息

Howard Hughes Medical Institute, Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, California, United States of America.

出版信息

PLoS One. 2007 Jun 13;2(6):e519. doi: 10.1371/journal.pone.0000519.

DOI:10.1371/journal.pone.0000519
PMID:17565372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1885217/
Abstract

BACKGROUND

The NuRD/Mi2 chromatin complex is involved in histone modifications and contains a large number of subunits, including the p66 protein. There are two mouse and human p66 paralogs, p66alpha and p66beta. The functions of these genes are not clear, in part because there are no mutants available, except in invertebrate model systems.

METHODOLOGY

We made loss of function mutants in the mouse p66alpha gene (mp66alpha, official name Gatad2a, MGI:2384585). We found that mp66alpha is essential for development, as mutant embryos die around day 10 of embryogenesis. The gene is not required for normal blastocyst development or for implantation. The phenotype of mutant embryos and the pattern of gene expression in mutants are consistent with a role of mp66alpha in gene silencing.

CONCLUSION

mp66alpha is an essential gene, required for early mouse development. The lethal phenotype supports a role in execution of methylated DNA silencing.

摘要

背景

NuRD/Mi2 染色质复合物参与组蛋白修饰，包含大量亚基，包括 p66 蛋白。有两种小鼠和人类的 p66 同源物，p66alpha 和 p66beta。这些基因的功能尚不清楚，部分原因是除了在无脊椎动物模型系统中，没有可用的突变体。

方法

我们在小鼠 p66alpha 基因（mp66alpha，官方名称 Gatad2a，MGI：2384585）中制造了功能丧失突变体。我们发现 mp66alpha 对发育是必需的，因为突变胚胎在胚胎发生的第 10 天左右死亡。该基因对于正常囊胚发育或植入并不必需。突变胚胎的表型和突变体中的基因表达模式一致表明 mp66alpha 在基因沉默中起作用。

结论

mp66alpha 是一个必需基因，对早期小鼠发育至关重要。致死表型支持其在甲基化 DNA 沉默的执行中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/bce72d93d4fd/pone.0000519.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/c1170b0f76f7/pone.0000519.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/20cb73bae611/pone.0000519.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/0bd4a1e60475/pone.0000519.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/5be558771fb8/pone.0000519.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/bce72d93d4fd/pone.0000519.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/c1170b0f76f7/pone.0000519.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/20cb73bae611/pone.0000519.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/0bd4a1e60475/pone.0000519.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/5be558771fb8/pone.0000519.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d78/1885217/bce72d93d4fd/pone.0000519.g005.jpg

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MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties.MBD2/NuRD和MBD3/NuRD是两种具有不同生化和功能特性的不同复合物。
p66α 通过作为 p53 的共激活因子来抑制乳腺癌细胞的生长和迁移。
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Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency.中和 Gatad2a-Chd4-Mbd3/NuRD 复合物有助于确定诱导起始多能性。
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Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90.绘制一种主要哺乳动物内质网热休克蛋白90的相互作用组图谱。
PLoS One. 2017 Jan 5;12(1):e0169260. doi: 10.1371/journal.pone.0169260. eCollection 2017.
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