基因表达调控.pptxVIP

基因表达调控第1页/共26页第2页/共26页知识点1 真核细胞基因表达的调控主要发生在四个相对独立的水平上[名词]基因表达调控：细胞使遗传信息在正确时间正确位置进行正确表达或关闭以行使特定功能的调节机制。真核细胞基因表达调控发生在4个彼此相对独立的水平上：1.转录水平：决定某个基因不否会被转录，什么时候转录，转录的频率。2.加式水平：决定初始的RNA转录产物如何剪接和加工为成熟的mRNA。3.翻译水平：决定某种mRNA是否会真正得到翻译，如果能得到翻译，决定翻译的频率和时间。4.翻译后水平：在蛋白被　翻译后，选择性激活蛋白或使蛋白失活。第3页/共26页知识点2 基因表达在转录水平上调控通用转录因子与结合RNA聚合酶的核心启动子位点结合，起始基础水平的转录。特异转录因子分为激活基因转录的激活型转录因子和抑制转录的抑制型转录因子，与基因的各种调控位点结合，促进或抑制基因转录。激素通过激活或抑制某些特异转录因子（激素受体）而影响基因转录。转录因子通常通过调节组蛋白核心结构而改变核小体和染色质紧密程度，影响通用转录因子和RNA聚合酶对启动子的结合来调节基因表达。激活型转录因子通常有利于导致染色质或组蛋白结构松散的蛋白质发挥作用，如组蛋白乙酰化酶；抑制型转录因子通过会加强促进染色质结构紧密的蛋白质作用，如组蛋白脱乙酰酶。第4页/共26页第5页/共26页Eukaryotic transcription of protein-encoding genes is a highly regulated process in which numerous transcription activators recognize specific DNA elements, proximal and distant to promoters, and direct assembly of general transcription factors, co-activator complexes and RNA polymerase II on promoters (the pre-initiation complex, at least 50 polypeptides). To understand the molecular mechanism of activator-dependent transcription initiation, one needs to understand the pathway of assembly of the pre-initiation complex, the structural organization of the pre-initiation complex, and how the assembly and structure of the pre-initiation complex are affected by binding of activators to cognate DNA elements – a very challenging task for traditional, ensemble, in vitro, methods 第6页/共26页Model of hormone-dependent gene activation by the glucocorticoid receptor (GR) In the absence of /bookshelf/?book=mcbpart=A7315rendertype=def-itemid=A7569hormone, GR is bound in a complex with Hsp90 in the /bookshelf/?book=mcbpart=A7315rendertype=def-itemid=A7436cytoplasm via its /bookshelf/?book=mcbpart=A7315rendertype=def-itemid=A7619ligand-binding /bookshelf/?book=mcbpart=A7315rendertype=def-itemid=A7459domain (light purple). When /bookshelf/?book=mcbpart=A7315rendertype=def-itemid=A7569hormone is present, it diffuses through the /bookshelf/?book=mcbpart=A7315rendertype=def-itemid=A7727plasma membrane and binds to the