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果蝇中人类HP1亚型的功能域分析

Functional domain analysis of human HP1 isoforms in Drosophila.

作者信息

Kato Masaki, Kato Yasuko, Nishida Miki, Hayakawa Tomohiro, Haraguchi Tokuko, Hiraoka Yasushi, H Inoue Yoshihiro, Yamaguchi Masamitsu

机构信息

Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, Japan.

出版信息

Cell Struct Funct. 2007;32(1):57-67. doi: 10.1247/csf.06032. Epub 2007 Jun 18.

DOI:10.1247/csf.06032
PMID:17575412
Abstract

Three subtypes of HP1, a conserved non-histone chromosomal protein enriched in heterochromatin, have been identified in humans, HP1alpha, beta and gamma. In the present study, we utilized a Drosophila system to characterize human HP1 functions. Over-expression of HP1beta in eye imaginal discs caused abnormally patterned eyes, with reduced numbers of ommatidia, and over-expression of HP1gamma in wing imaginal discs caused abnormal wings, in which L4 veins were gapped. These phenotypes were specific to the HP1 subtypes and appear to reflect suppressed gene expression. To determine the molecular domains of HP1 required for each specific phenotype, we constructed a series of chimeric molecules with HP1beta and HP1gamma. Our data show that the C-terminal chromo shadow domain (CSD) of HP1gamma is necessary for HP1gamma-type phenotype, whereas for the HP1beta-type phenotype both the chromo domain and the CSD are required. These results suggest human HP1 subtypes use different domains to suppress gene expression in Drosophila cells.

摘要

异染色质中富集的一种保守的非组蛋白染色体蛋白HP1在人类中有三种亚型,即HP1α、β和γ。在本研究中,我们利用果蝇系统来表征人类HP1的功能。在眼成虫盘过表达HP1β导致眼睛图案异常,小眼数量减少,而在翅成虫盘过表达HP1γ导致翅膀异常,其中L4翅脉有间隙。这些表型是HP1亚型特有的,似乎反映了基因表达受到抑制。为了确定每种特定表型所需的HP1分子结构域,我们构建了一系列HP1β和HP1γ的嵌合分子。我们的数据表明,HP1γ的C端染色质影域(CSD)对于HP1γ型表型是必需的,而对于HP1β型表型,染色质域和CSD都是必需的。这些结果表明,人类HP1亚型在果蝇细胞中利用不同的结构域来抑制基因表达。

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1
Functional domain analysis of human HP1 isoforms in Drosophila.果蝇中人类HP1亚型的功能域分析
Cell Struct Funct. 2007;32(1):57-67. doi: 10.1247/csf.06032. Epub 2007 Jun 18.
2
Cell cycle behavior of human HP1 subtypes: distinct molecular domains of HP1 are required for their centromeric localization during interphase and metaphase.人类HP1亚型的细胞周期行为:在间期和中期,HP1的不同分子结构域对于其着丝粒定位是必需的。
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Functional analysis of the chromo domain of HP1.异染色质蛋白1(HP1)染色体结构域的功能分析
EMBO J. 1995 Aug 15;14(16):3977-86. doi: 10.1002/j.1460-2075.1995.tb00069.x.
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Expression and functional analysis of three isoforms of human heterochromatin-associated protein HP1 in Drosophila.人类异染色质相关蛋白HP1三种异构体在果蝇中的表达及功能分析
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The HP1 chromo shadow domain binds a consensus peptide pentamer.HP1染色体阴影结构域结合一个共有肽五聚体。
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Pericentromeric heterochromatin domains are maintained without accumulation of HP1.着丝粒周围的异染色质结构域得以维持,而HP1没有积累。
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The hinge and chromo shadow domain impart distinct targeting of HP1-like proteins.铰链区和染色质结构域赋予类HP1蛋白不同的靶向性。
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The chromo shadow domain, a second chromo domain in heterochromatin-binding protein 1, HP1.染色质阴影结构域,异染色质结合蛋白1(HP1)中的第二个染色质结构域。
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Dynamic and selective interactions of the transcriptional corepressor TIF1 beta with the heterochromatin protein HP1 isotypes during cell differentiation.转录共抑制因子TIF1β与异染色质蛋白HP1亚型在细胞分化过程中的动态选择性相互作用。
Differentiation. 2007 Sep;75(7):627-37. doi: 10.1111/j.1432-0436.2007.00166.x. Epub 2007 Mar 23.

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Hum Genet. 2020 Feb;139(2):151-184. doi: 10.1007/s00439-019-02095-5. Epub 2019 Dec 3.
2
Mechanisms of functional promiscuity by HP1 proteins.HP1蛋白的功能混杂机制。
Trends Cell Biol. 2014 Jun;24(6):377-86. doi: 10.1016/j.tcb.2014.01.002. Epub 2014 Mar 4.
3
Drosophila HP1c is regulated by an auto-regulatory feedback loop through its binding partner Woc.
果蝇HP1c通过其结合伴侣Woc受自身调节反馈环调控。
PLoS One. 2009;4(4):e5089. doi: 10.1371/journal.pone.0005089. Epub 2009 Apr 7.