Section outline

  • lesson content

    What turns a gene on?
    ::是什么让基因打开的?

    Many times it involves a binding to . Shown here is a model of p53 protein bound to DNA. p53 is a transcription factor whose inactivation can trigger the onset of .
    ::有很多次它涉及到对.的约束。这里显示的是一种P53蛋白质的模型,它与DNA联系在一起。p53是一个转录系数,不活动可以触发 。

    Mechanisms of Gene Regulation
    ::基因管制机制

    Any step of gene expression may be modulated, from the initiation of to the post-translational modification of a protein. Following is a list of stages where gene expression is regulated:
    ::基因表达的任何步骤都可以调整,从蛋白质的开始到翻译后修改。

    • Chemical and structural modification of DNA or chromatin .
      ::DNA或染色体的化学和结构改变。
    • Transcription.
      ::解密 。
    • .
    • Post-transcriptional modification.
      ::事后改写。
    • transport.
      ::运输。
    • mRNA degradation.
      ::mRNA 降解。
    • Post-translational modifications.
      ::翻译后修改。

    In this concept, we will focus on regulation at the level of transcription. During transcription, RNA polymerase binds to a gene and reads the DNA template to make a complementary strand of RNA. How does RNA polymerase know which genes to bind to, when to bind to those genes, and where on the gene to bind? Concerning the binding of RNA polymerase, the which, when and where is a highly regulated process. When RNA polymerase binds to a gene, it binds to the promoter , a segment of DNA that allows a gene to be transcribed. The promoter helps RNA polymerase find the start of a gene.
    ::在这个概念中,我们将侧重于对转录层次的监管。在转录过程中,RNA聚合酶与基因结合,并阅读DNA模板,以形成RNA的互补性。RNA聚合酶如何知道哪些基因结合,何时与这些基因结合,以及基因连接到何处?关于RNA聚合酶的结合,这种结合是一个高度规范的过程,何时何地和何地。当RNA聚合酶与基因结合时,它与促销者结合,一个允许基因转录的DNA部分。促进者帮助RNA聚合酶找到基因的开端。

    Cis and Trans
    ::Cis 和 Trans

    Gene regulation at the level of transcription controls when transcription occurs as well as how much RNA is created. This regulation is controlled by cis- regulatory elements ( cis from the Latin word meaning "on the same side as") and trans-acting factors ( trans from the Latin root meaning "across from"). A cis-regulatory element is a region of DNA which regulates the expression of a gene or multiple genes located on that same strand of DNA. These cis-regulatory elements are often the binding sites of one or more trans-acting factors, usually a regulatory protein which interacts with RNA polymerase. A cis-regulatory element may be located in a gene’s promoter region, in an intron , or in the 3' region. A regulatory protein , or a transcription factor , is a protein involved in regulating gene expression. It is usually bound to a cis-regulatory element. Regulatory proteins often must be bound to a cis-regulatory element to switch a gene on (activator), or to turn a gene off (repressor). Common cis-regulatory elements include the TATA box , Pribnow box and CCAAT box. More about will be discussed in the Regulation of Gene Expression: Transcription Factors (Advanced) concept.
    ::在转录时进行基因调控,以及创造多少RNA。这种调控由cis-调控元素(拉丁词的意思是“与”相同侧面)和转基因因素(来自拉丁根系的意思是“交错”)加以控制。一个cis-调控元素是DNA的一个区域,它管理着基因或同一端DNA上的多个基因的表达方式。这些调控元素往往是一个或多个转基因因素的束缚点,通常是与RNA聚合酶发生相互作用的调控蛋白质。一个Cis-调控元素可能位于基因促销区域、一个内线或3'区域。一种调控蛋白质或转基因表达方式涉及一种蛋白质。它通常与一个精致调元素联系在一起。监管蛋白通常必须与一个精致调元素捆绑在一起,以转换基因(活化器),或关闭基因(压缩机)。常见的Cis-调控元素包括TATA框、Pribnow 框和TRAT。关于GENDA的调制(GENA)将讨论。

    The TATA Box
    ::TATATA 框框

    The TATA box is a cis-regulatory element found in the promoter region of genes in and eukaryotes . It is a highly conserved sequence, believed to have remained consistent throughout much of the evolution. Approximately 24% of human genes contain a TATA box within the core promoter. The TATA box has the core DNA sequence 5'-TATAAA-3' or a slight variant. It is usually located 25 base pairs upstream of the transcription start site. During transcription, the TATA binding protein binds to the TATA box. This protein helps unwind the DNA double helix , allowing RNA polymerase II to bind and begin transcription.
    ::TATA框是一个CIS-调控元素,在突变基因和eukaryotes基因的推广区发现。它是一个高度节制的序列,据信在整个进化过程中一直保持一贯性。大约24%的人类基因在核心推进器中含有TATA框。TATA框有DNA核心序列 5'TATAAA-3'或一个微变体。它通常位于转录起始点上游的25对基底对。在转录过程中,TATA将蛋白结合到TATA盒中。这种蛋白质有助于解开DNA双螺旋,使RNA聚合酶II能够捆绑并开始转录。

    However, prior to RNA polymerase binding to the promoter, the TATA binding protein interacts with other factors to form TFIID, a general transcription factor that is part of the RNA polymerase II preinitiation complex. TFIIA binds to the upstream part of TFIID while TFIIB binds to the downstream part of TFIID. Now RNA polymerase recognizes this multi-protein complex and binds to it, along with various other transcription factors, initiating transcription. RNA polymerase moves along the DNA strand, leaving TFIID and TFIIA bound to the TATA box where they can then facilitate the binding of additional RNA polymerase II molecules.
    ::然而,在对促销者具有约束力的RNA聚合酶之前,TATA粘合蛋白与其他因素相互作用,形成TFID,这是RNA聚合酶II的启动综合体的一部分。TFIIA与TFIID的上游部分捆绑,TFIIB与TFIID的下游部分捆绑。现在RNA聚合酶承认这种多蛋白复合体,并与其他各种转录因素一起捆绑在一起,开始转录。RNA聚合酶沿DNA链条移动,使TFIID和TFIIA受TATA盒的约束,从而便利附加RNA聚合酶II分子的约束。

    The complex of RNA polymerase II and various transcription factors is known as a basal transcriptional complex (BTC) . The BTC only provides a low level of transcription. Other cis and trans factors must stimulate the BTC to increase transcription levels. One such example of a BTC stimulating region of DNA is the CAAT box.
    ::RNA聚合酶II的综合体和各种转录因数被称为一个管状转录综合体(BTC),BTC只提供低水平的转录,其他的转录和转录因素必须刺激BTC增加转录水平,BTC刺激DNA区域的一个实例就是CAAT箱。

    The Pribnow Box
    ::普里布诺盒子

    The Pribnow box is the sequence of six nucleotides that is an essential part of a promoter site in . The sequence 5'-TATAAT-3' is the most common, though slight variants of that sequence serve the same function. It is located roughly 10 base pairs upstream from transcription initiation site. The Pribnow box has a function similar to the TATA box that occurs in promoters in eukaryotes and archaea. The regulation of transcription in prokaryotic is much simpler than in eukaryotes, and many fewer transcription factors, if any, are necessary. In bacteria, this site is recognized and bound by a subunit of RNA polymerase during initiation of transcription.
    ::Pribnow箱是6个核糖核酸的序列,这是 5'-TATAT-3' 序列是最常见的,尽管该序列的细微变异功能相同。它位于从转录启动站向上游大约10对基对。Pribnow 盒的功能类似于在eukaryotes和Artaea 的推介器中出现的TATA箱。对 prokaryotes 转录的规范比eukaryotes 简单得多,如果需要的话,也少得多。在细菌中,这个站点在转录启动时被RNA聚合酶的子单位承认和约束。

    The Pribnow box, like the TATA box, is the initial site where hydrogen bonds between the DNA strands are separated. The AT-rich character of the two boxes allows this separation, as adenine and thymine are easier to separate then cytosine-guanine base pairs.
    ::Pribnow盒子和TATA盒子一样,是将DNA线之间的氢系隔开的最初地点。 这两个箱子中具有丰富的ATT特性使得这种分离成为可能,因为和胸腺比较容易分离,然后是细胞氨基底对。

    The CCAAT Box
    ::CCAAT箱

    The CCAAT Box , which is also known as the CAAT box or CAT box, is an eukaryotic cis-regulatory element with a 5'-GGCCAATCT-3' consensus sequence. It occurs roughly 75-80 bases upstream of the initial transcription site. This site is known to bind general transcription factors, including the CCAAT-enhancer-binding proteins (C/EBPs). The C/EBPs recruit additional transcription factors to the initiation complex . C/EBPs are characterized by a highly conserved basic- leucine zipper . This domain is involved in dimerization and DNA binding like other transcription factors of the leucine zipper domain-containing family, including c-Fos and Jun. Other DNA binding domains include the helix-turn-helix domain, the zinc finger domain and the helix-loop helix domain. These domains are further discussed in the Regulation of Gene Expression: Transcription Factors (Advanced) concept.
    ::CCAAT箱(又称CAAT箱或CAT箱)是一个有5'-GGCAATCT-3'协商一致顺序的防腐调控元素,在最初转录站的上游大约75-80个基点,该站点将一般转录因数捆绑起来,包括CADAT-Ehancer-有约束力蛋白质(C/EBPs);C/EBPs为启动综合体招聘了额外的转录因数。C/EBPs的特点是具有高度保存的基本液态拉链。这个域与Leucine lipper 包含域的家族(包括c-Fos和Jun)的其他转录因数一样,也涉及分解和DNA结合因素。其他DNA约束域包括螺旋-转弯-Helix域、锌手指域和螺旋螺旋螺旋体螺旋体域。这些域在《基因表达条例》中进一步讨论:转录因因素(Advanced)概念中。

    Mechanisms of Transcriptional Regulation
    ::临时管制机制

    Transcription of a gene by RNA polymerase can be regulated by at least five mechanisms:
    ::由RNA聚合酶对基因的移植至少可以通过五个机制加以管制:

    • Specificity factors are proteins that alter the specificity of RNA polymerase for a promoter or set of promoters, making it more or less likely to bind to the promoter and begin transcription.
      ::具体因素是蛋白质,这些蛋白质改变了RNA聚合酶对促销者或成套促销者的特殊性,使得它或多或少有可能与促销者捆绑并开始转录。
    • Repressors are proteins that bind to non-coding sequences on the DNA that are close to or overlap the promoter region, impeding RNA polymerase's progress along the strand.
      ::压缩机是蛋白质,与DNA上的非编码序列相连,接近或重叠于促销区,阻碍RNA聚合酶沿链条的进展。
    • Basal factors are transcription factors that help position RNA polymerase at the start of a gene.
      ::Basal因素是转录系数,有助于RNA聚合酶在基因初始的位置。
    • Enhancers are sites on the DNA strand that are bound by activators in order to loop the DNA, bringing a specific promoter to the initiation complex. An initiation complex is composed of RNA polymerase and numerous trans-acting factors.
      ::增强器是DNA线上的站点,它们受活性剂的约束,以便连接DNA,将特定的促进器带入启动综合体,启动综合体由RNA聚合酶和许多中转反应因素组成。
    • Activators are proteins that enhance the interaction between RNA polymerase and a particular promoter.
      ::活性剂是蛋白质,可增强RNA聚合酶与某一特定促销者之间的互动。

    As the organism grows more sophisticated, gene regulation becomes more complex, though prokaryotic organisms possess some highly regulated systems. Some human genes are controlled by many activators and repressors working together. Obviously, a in a cis-regulatory region, such as the promoter, can greatly affect the proper expression of a gene. It may keep the gene permanently off, such that no protein can be made, or it can keep the gene permanently on, such that the corresponding protein is constantly made. Both of these can have detremental effects on the .
    ::随着有机体的日益成熟,基因监管变得更加复杂,尽管蛋白质生物拥有一些高度监管的系统。 有些人类基因由许多活性者和抑制者共同控制。 显然,在像促进者这样的Cis-监管区,可以极大地影响基因的正确表达方式。 它可以永久保存基因,从而无法制造蛋白质,或者可以永久保存基因,从而不断制造相应的蛋白质。 这两种基因都会对基因产生分泌效应。

    lesson content

    Regulation of Transcription. Regulatory proteins bind to regulatory elements to control transcription. The regulatory elements are embedded within the DNA.
    ::监管监管:监管性蛋白质受监管要素约束,以控制转录,监管要素嵌入DNA。

    Summary
    ::摘要

    • A cis-regulatory element is a region of DNA which regulates the expression of a gene or multiple genes located on that same strand of DNA.
      ::精密调控元素是DNA区域,对同一DNA线上的基因或多种基因的表达方式进行规范。
    • The cis-regulatory elements are often binding sites for one or more trans-acting factors, usually a regulatory protein which interacts with RNA polymerase.
      ::精密调控元素往往是一种或多种中转因素的约束场所,通常是一种与RNA聚合酶相互作用的调节蛋白。
    • Repressor proteins bind to non-coding sequences on the DNA that are close to or overlap the promoter region, impeding RNA polymerase's progress along the strand.
      ::压缩蛋白质与DNA上接近或重叠的脱氧核糖核酸非编码序列捆绑在一起,阻碍RNA聚合酶沿链条的进展。
    • Enhancers are sites on the DNA strand that are bound by activators.
      ::增强剂是DNA线上受活性剂约束的强化剂。
    • Common cis-regulatory elements include the TATA box, Pribnow box and CCAAT box.
      ::共同的手续管理要素包括TATA箱、Pribnow箱和CCAAT箱。

    Review
    ::回顾

    1. How do cis-regulatory elements and a trans-acting factors work together?
      ::如何使手续管制要素和交易因素相互配合?
    2. Define a transcription factor.
      ::界定转录系数。
    3. Describe common cis-regulatory elements.
      ::描述共同的特许管理要素。
    4. Compare the TATA box, Pribnow box and CCAAT box.
      ::比较TATA盒子、Pribnow盒子和CCAAT盒子。
    5. Identify the five mechanisms of transcriptional regulation.
      ::确定五个转录监管机制。