组蛋白乙酰化
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(3)、As a special signal, the histone acetylation and deacetylation can be identified and influenced by other protein factors, in order to achieve the regulation of gene expression.
the histone deacetylase, HDAC
组蛋白去乙酰化酶
It's a classical protease, which plays an important role in chromosome structural modification and the regulation of gene expression.
(3)、The histone acetylation and
deacetylation can be identified and influenced by other protein factors
组蛋白乙酰化、去乙酰化并不能直接引起染色质结构的改
变,也不能使核小体滑动。而是通过招募染色质构型重建复合 体并与其协同作用引起染色质构型改变的。组蛋白乙酰化甚至 是其它转录因子活动的前提。 如:H4第8位赖氨酸的乙酰化是招募SWI/SNF所必须的,而 H3的第9和14位赖氨酸的乙酰化则是招募TFIID的关键。HDACs可 与多种转录因子或辅因子相互作用,如几乎所有第II类HDACs都 能与DNA结合的转录因子(包括MEF2,BCL6,PLZF,TR2等)、转录 辅抑制因子(如N-CoR,SMRT,BcoR,CtBP等)相互作用而参与转 录的激活或抑制。HDACs也可以和DNA甲基化酶(DNA Methyltransferases,DNMT)、组蛋白甲基化酶(Histone Methyltransferases,HMT)等结合,共同被转录抑制因子招募, 参与基因转录抑制。
(2)、The histone acetylation and
deacetylation change the chromatin configuration 许多试验证明,在哺乳动物细胞中,HATs可促进SWI/SNF连
接到染色体上并维持其稳定,核小体组蛋白乙酰化后才能被 SWI/SNF的溴域(许多染色质构型重建复合体和转录因子或辅因 子都具有这一结构)识别并结合到乙酰化了的组蛋白上发挥其 作用。 此外,有些ATP依赖的染色质构型重建复合体本身就具有 HDAC活性,如HDAC1和HDAC2共同构成Sin3、Mi-2/NuRD和CoREST 的催化核心,HDAC3则是N-CoR和SMRT的催化亚基。因而,Mi2/NuRD在染色质构型重建中作用的发挥离不开组蛋白去 乙酰化酶,同样hSWI/SNF需与Sin3及CoREST结合发挥作用,转 录抑制因子通过依次招募CoR-EST、Sin3和hSWI/SNF形成封闭的 染色质结构而抑制转录。另外,HDAC1还与DNA拓扑异构酶II相 互作用,使染色形成紧密的结构导致基因沉默。
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(1)、The histone acetylation and deacetylation change the surrounding environment of nucleosomes'
在组蛋白八聚体形成的过程中,多数组蛋白的C末端氨基
酸包裹在八聚体里面,N末端氨基酸则伸向外面形成“组蛋白尾 巴”。 这个“组蛋白尾巴”易发生多种共价修饰(常见的是:乙 酰化),核小体组蛋白的乙酰化中和了其周围的正电荷,增加 了组蛋白的亲水性,削弱了组蛋白与DNA的相互作用,而使染色 质处于相对松弛的状态,利于转录因子与DNA的结合。
3、regulation
It's considered that the histone acetylation and deacetylation affecwenku.baidu.coms gene expression primarily through the following ways.
(1)、The histone acetylation and deacetylation change the surrounding environment of nucleosomes', and strengthen or weaken the interaction of the protein and DNA in the gene expression.
关转录因子(如NF-kB、IRFs、ATF-2等)结合到核心核小体外 的增强子上,形成增强子复合体,由这个复合体招募Gen5,使 核小体组蛋白H3的第9位和H4第8位赖氨酸乙酰化,SWI/SNF识 别并结合到CBP(CREB Binding Protein)和乙酰化了的核小体 上,通过一种尚未明确的机制改变染色质构型,使TFIID连接到 TATA盒上形成转录起始复合物。
相反,组蛋白的去乙酰化则使核小体周围带正电荷增加,
与DNA的磷酸基所带负电荷的相互作用加强,染色质结构变得紧 密而不利于转录。这可能是组蛋白乙酰化、去乙酰化参与基因 表达调控的机制之一,也能较好的解释和支持组蛋白乙酰化促 进基因活化,而去乙酰化参与基因沉默的观点。
(2)、The histone acetylation and
deacetylation change the chromatin configuration
HATs(组蛋白乙酰化酶)使组蛋白尾巴乙酰化,形成“开 放”的染色质结构,便于转录进行;相反,HDACs(组蛋白去 乙酰化酶)使组蛋白去乙酰后,染色质形成“封闭”结构,导 致“基因沉默”。
如:在INF-b基因转录起始复合物形成过程中,首先是相
4、The histone acetylation
and deacetylation & lung cancer
The histone deacetylase(组蛋白去乙酰化酶, HDAC) play
a decisive role in tumorigenesis, such as in lung cancer. Nowadays a viable method for study this project, is to detect the level of HDAC1 mRNA.
Gene expression
The Acetylation of Histone
as cancer is a common disease we can not suppress
2、The basic theory of
Acetylation
Acetylation is the introduction of nitrogen, oxygen, carbon atoms on to the acetyl group CH3CO- in the organic compound moleculs. Commonly used acetyl chloride and acetic anhydride as acetylating agent.
The Acetylation
of Histone
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1、Introduction:
Acetylation
Acetylation in clinical medicine such as cancer
The chromosome is consisted by DNA and Histone
(3)、The histone acetylation and
deacetylation can be identified and influenced by other protein factors
组蛋白乙酰化/去乙酰化也受其它蛋白质活动的影响,转录 激活因子(或抑制因子)可招募HATs(或HDACs)复合物到基因 启动子区使特定组蛋白乙酰化或去乙酰化。另外,基因启动子 附近组蛋白高甲基化可招募HATs,增强基因表达;而低甲基化 可招募HDACs抑制基因表达。 某些转录因子也具有调节HAT活性的功能,例如:病毒癌蛋 白SV40的T抗原可以增强HAT的活性。HATs和HDACs本身也可被 修饰,如酪蛋白激酶2(CK2)可使HDAC1和HDAC2特殊位点磷酸 化而调节其活性;具有HATs活性的ATCR可被P300/CBP乙酰化, P/CAF不仅可被其它HAT乙酰化,还能使自身乙酰化,而且P/CAF 的乙酰化可增强其自身的活性。此外,已发现多种外源性物质 (如丁酸盐、TSA、FK228等)可抑制HDACs的活性,影响多种 基因的表达,而具有抗肿瘤作用。
CH3CH2OH(乙醇)+CH3COCL(氯乙酰)→CH3COO· CH2CH3 (醋酸乙酯) +HCL NH3(氨)+(CH3CO)2O(醋酸酐)→CH3CONH2(乙酰胺)+CH3COOH(醋酸)
the Acetylation in the life sciences It's the process of the transform of acetyl into the amino acid side chain groups, the most common one is the histone acetylation.
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(2)、The histone acetylation and deacetylation change the chromatin configuration, thereby to affect protein-protein, protein and DNA interactions.
In the nucleus, histone acetylation and histone deacetylation process is in dynamic equilibrium. And is a common regulation, by histone acetyltransferase(组蛋白乙酰化 转移酶, HAT)and histone deacetylase (组蛋白去乙酰化酶, HDAC)
Under normal circumstances, the acetylation
of histones is conducive to the dissociation of DNA and histone octamer, and help to relax the nucleosome structure. So that a variety of transcription factors and synergistic transcription factors can specific binding to the binding sites of DNA, and activate the gene transcription.
histone deacetylase inhibitors (组蛋白去乙酰化酶抑制剂,HDACi)
The HDAC overexpression in cancer cells lead to enhance the role of deacetylation. Through the restoration of the positively charged of histone, to increase the gravitational attraction between the DNA and histones, to make the nucleosomes become close, and is not conducive to the expression of specific genes, including some tumor suppressor genes.