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组蛋白甲基化

Reference: Genes IX (Benjamin Lewin) 现代分子生物学 (朱玉贤)
Regulation of Gene Expression
Chromatin
epigenetic control
Protein degradation RNA silencing
一般而言的基因表达调控范畴
Part I: Histone modifications
组蛋白的化学修饰
组蛋白化学修饰发生在组蛋白N端尾部,尤其是组蛋白H3 和H4的修饰起始了 染色质结构的变化。组蛋白N端尾部从 DNA转弯处的核小体间延伸出来。
组蛋白化学修饰的类型
组蛋白乙酰化 Lysine (K) Acetylation 组蛋白甲基化 Lysine (K), Arginine (R) Methylation 组蛋白磷酸化 Serine (S), Threonine (T) Phosphorylation 组蛋白泛素化 Lysine (K) Ubiquitination
Histone Code
组蛋白密码
相对而言,组蛋白的甲基化修饰方式是最稳定的,所以最 适合作为稳定的表观遗传信息。而乙酰化修饰具有较高的 动态,另外还有其他不稳定的修饰方式,如磷酸化、腺苷 酸化、泛素化、SUMO化、ADP核糖基化等等。这些修饰更 为灵活的影响染色质的结构与功能,通过多种修饰方式的 组合发挥其调控功能。所以有人称这些能被专识别的修饰 信息为组蛋白密码。这些组蛋白密码组合变化非常多,因 此组蛋白共价修饰可能是更为精细的基因表达方式。
Promoter activation involves binding of a sequence-specific activator, recruitment and action of a remodeling complex, and recruitment and action of an acetylating complex.
The heart of the remodeling complex is its ATPase subunit. Remodeling complexes are usually classified according to the type of ATPase subunit
A remodeling complex binds to chromatin via an activator (or repressor)
组蛋白SUMO化 Lysine (K) Sumoylation 组蛋白糖基化 Glutamate, Arginine (R) ADP-Ribosylation
有些化学修饰的化学基团可以减少组蛋白的正电性,从而使其与DNA 结合变疏松,使染色质结构发生变化。
histone acetylation and histone phosphorylation change the overall charge of the chromatin structure. These modifications can lead to a general decondensation of the chromatin fibre.
Transcriptional Regulation of Eukaryotic Genes (真核基因的转录调控) 1.Transcriptional initiation 2.Histone modification 3.DNA methylation
Post-Transcriptional Regulation of Eukaryotic Genes (真核基因的转录后调控) 1.siRNA and RNA silencing 2.miRNA and other ncRNA
Chromatin remodeling
The dynamic model for transcription of chromatin relies upon factors that can use energy provided by hydrolysis of ATP to displace nucleosomes from specific DNA sequences.
A genomic survey suggested that most sites that bind transcription factors are free of nucleosome.
In addition to chromatin remodeling, chemical modifications on histones also play a central role in gene regulation
Nucleosome (核小体) 是染色质的基本结构 单位,由~200 bp DNA和组蛋白八聚体组成
Nucleosomes are hard to get access
If nucleosomes form at a promoter, transcription factors (and RNA polymerase) cannot bind. If transcription factors (and RNA polymerase) bind to the promoter to establish a stable complex for initiation, histones are excluded.
two major types of chromatin remodeling complex: SWI/SNF and ISW (imitation SWI)
Chromatin remodeling is undertaken by large complexes that use ATP hydrolysis to provide the energy for remodelinபைடு நூலகம்.
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