The transposon-driven evolutionary origin and basis of histone deacetylase functions and limitations in disease prevention.
The transposon-driven evolutionary origin and basis of histone deacetylase functions and limitations in disease prevention.
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DOI：
10.1007/s13148-011-0020-z
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发表时间：
2011-08
影响因子：
5.7
通讯作者：
Tollefsbol, Trygve O.
中科院分区：
文献类型：
--
作者：
Peek, Gregory W.;Tollefsbol, Trygve O.
组蛋白去乙酰化酶（HDACs）与原核生物的酶具有同源性，在真核生物组蛋白进化之前，这些原核生物的酶就已能从非组蛋白蛋白质上去除乙酰基。从原核生物或共同祖先遗传下来的酶，逐渐适应了对组蛋白进行去乙酰化作用，同时对非组蛋白蛋白质进行的有益去乙酰化作用也被选择性地保留了下来。组蛋白去乙酰化作用可防止产生具有病理后果的转录，包括病毒DNA的表达，以及随机转座子插入导致的重要基因缺失或失调。据信，病毒是从转座子进化而来的，转座子为HDAC的进化提供了最初的推动力。由于转座子插入可能影响的基因范围广泛，HDACs能够预防的疾病种类也极为繁多。可能阻止转录的染色质抑制性修饰还包括组蛋白H3和H4特定赖氨酸残基的甲基化，以及在特定组蛋白赖氨酸甲基化之后特定DNA胞嘧啶的甲基化。单个组蛋白残基的甲基化和乙酰化是相互排斥的。虽然转座子是HDAC进化过程中需要预防的疾病来源，但它们也是通过 “分子驯化” 招募的众多有价值的编码和调控序列的来源。这些序列有助于形成复杂的转录调控机制，在这种机制中，具有相反作用的成分，如HDACs和组蛋白乙酰转移酶（HATs），可能会相互协调和互补。然而，在复杂的转录调控中，HDACs对于某些关键的感染性和非感染性疾病仍然无法起到防御作用，因为进化上的妥协使得它们的活性具有短暂性。
Histone deacetylases (HDACs) are homologous to prokaryotic enzymes that removed acetyl groups from non-histone proteins before the evolution of eukaryotic histones. Enzymes inherited from prokaryotes or from a common ancestor were adapted for histone deacetylation, while useful deacetylation of non-histone proteins was selectively retained. Histone deacetylation served to prevent transcriptions with pathological consequences, including the expression of viral DNA and the deletion or dysregulation of vital genes by random transposon insertions. Viruses are believed to have evolved from transposons, with transposons providing the earliest impetus of HDAC evolution. Because of the wide range of genes potentially affected by transposon insertions, the range of diseases that can be prevented by HDACs is vast and inclusive. Repressive chromatin modifications that may prevent transcription also include methylation of selective lysine residues of histones H3 and H4 and the methylation of selective DNA cytosines following specific histone lysine methylation. Methylation and acetylation of individual histone residues are mutually exclusive. While transposons were sources of disease to be prevented by HDAC evolution, they were also the source of numerous and valuable coding and regulatory sequences recruited by “molecular domestication.” Those sequences contribute to evolved complex transcription regulation in which components with contradictory effects, such as HDACs and HATs, may be coordinated and complementary. Within complex transcription regulation, however, HDACs remain ineffective as defense against some critical infectious and non-infectious diseases because evolutionary compromises have rendered their activity transient.
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DOI：
10.1097/qad.0b013e32832ec1dc
发表时间：
2009-09-10
期刊：
AIDS (London, England)
影响因子：
--
作者：
Archin NM;Keedy KS;Espeseth A;Dang H;Hazuda DJ;Margolis DM
通讯作者：
Margolis DM
影响因子：
4.6
作者：
Chou, Chao-Kai;Lee, Dung-Fang;Sun, Hui-Lung;Li, Long-Yuan;Lin, Chun-Yi;Huang, Wei-Chien;Hsu, Jung-Mao;Kuo, Hsu-Ping;Yamaguchi, Hirohito;Wang, Ying-Nai;Liu, Mo;Wu, Hsin-Yi;Liao, Pao-Chi;Yen, Chia-Jui;Hung, Mien-Chie
通讯作者：
Hung, Mien-Chie
影响因子：
4.7
作者：
Chawla, S;Vanhoutte, P;Bading, H
通讯作者：
Bading, H
影响因子：
6.2
作者：
Bowman, Mary-Catherine;Archin, Nancie M.;Margolis, David M.
通讯作者：
Margolis, David M.
影响因子：
64.8
作者：
Alland, L;Muhle, R;DePinho, RA
通讯作者：
DePinho, RA