Name: how eukaryotic gene repressors work
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 1 min 52 s
Channel: JoVE

转录抑制剂 有能力压抑 基因的转录。它们有一个独特的 域来绑定 调节序列 DNA和另一个域 能抑制转录。这些蛋白质可以 抑制转录 通过各种机制。最简单的是 阻止激活剂 从绑定到它的 顺式调控序列 通过几个 不同的机制。在某些情况下，竞争性抑制 绑定到 调节顺序，从而防止 激活剂的结合。在其它情况下，抑制剂会结合 到激活器附近的站点 绑定站点，它是 阻遏物域相互作用 与激活剂 阻止它绑定 调节顺序。抑制剂也可以 竞争约束 到通用转录的 结合位点 DNA上的因素 并阻止组装 转录的 机械。抑制剂也可以结合 自己抑制顺式 调控序列，预防 转录的启动 即使在场 激活剂 在调节区域。其中最通用的 机制之一 通过转录使用 抑制剂是 使用其阻遏物域 募集已知的蛋白质 作为共同抑制者。共同抑制因素通常有 酶促活动 可以抑制转录。许多协同阻遏物功能 作为组蛋白脱乙酰基酶 组蛋白甲基转移酶，和其它染色质重塑剂。这些修改结果 在紧密包装中 核小体中的DNA 并限制访问 转录 因素和聚合酶 到它们的调控 位点，从而 抑制转录。

<ol>
	<li>Lodish H， Berk A， Zipursky SL， et al. 分子细胞生物学。第 4 版。纽约:W. H. Freeman;2000. 第 10.7 节，真核生物转录控制的分子机制。可从: https://www.ncbi.nlm.nih.gov/books/NBK21677/</li>
	<li>Hanna-Rose， W.， & Hansen， U. （1996年）。真核生物转录抑制因子的主动抑制机制。遗传学趋势，12（6），229-234。doi:10.1016/0168-9525（96）10022-6</li>
	<li>伦卡维茨，R.（1990 年）。真核生物的转录抑制。遗传学趋势， 6， 192-196。doi:10.1016/0168-9525（90）90176-7</li>
</ol>

真核转录抑制因子

Eukaryotic Transcription Inhibitors

某些生化过程，例如胚胎发育和细胞生长调节，取决于特定基因的抑制。 DNA 结合蛋白（称为真核转录抑制剂）调节真核生物中基因表达的抑制。 这些抑制因子在细胞中所需的位置和时间的存在是由激素的存在和来自其他细胞的额外信号触发的。

真核转录抑制因子通常包含两个不同的结构域，一个DNA结合结构域和一个阻遏结构域。 转录抑制因子的阻遏物结构域可以与其他蛋白结合，例如基础转录调节子、激活子、共激活子和共阻遏物。 抑制结构域可以根据其组成氨基酸进行模糊分类，例如富含丙氨酸的结构域、富含谷氨酰胺的结构域和富含脯氨酸的结构域。 它们还可以分为酸性或碱性结构域，以及亲水性或疏水性结构域。 这些结构域通常是可互换的，并且不同的阻遏物结构域可以与相同的 DNA 结合结构域相关联。

真核转录抑制因子可以通过三种主要机制发挥其功能——抑制DNA结合、阻断激活和基因沉默。

DNA 结合的抑制可以防止激活因子与启动子或增强子位点结合，也可以防止转录起始复合物与转录起始位点或 TATA 盒结合。 这可以通过抑制因子与调控位点或起始位点的结合或通过抑制结构域与激活因子、共激活因子或参与转录机制的蛋白的结合来发生。 例如，在人类中，转录抑制因子 NF-E 与胎儿 γ-珠蛋白基因的 CCAAT 盒结合，并抑制激活因子 CP1 的结合。

阻断激活可防止来自与启动子或增强子结合的转录激活子的信号到达转录起始位点。 当抑制因子结合到启动子或增强子附近的位点时，例如在 c-myc 的调节中，抑制因子myc-PRF 结合到启动子旁边，就会发生这种情况。 这种抑制也可以通过抑制因子结合到DNA结合的激活因子而发生。在酵母中，当抑制因子GAL80与激活因子GAL4结合到启动子上时，就会发生这种类型的抑制。

当抑制因子通过同时结合构成该机制的蛋白之一和靠近转录起始位点的 DNA 上的一个位点来锁定或破坏转录起始复合物时，就会发生基因沉默，从而锚定转录机制。 例如，在酵母中，抑制因子 α-2 通过作为二聚体与激活因子 GRM 以及与 GRM 结合位点边界的 DNA 序列结合，使交配型 a 特异性基因失活。

某些生化过程，如胚胎发育和细胞生长调控，依赖于特定基因的抑制。DNA 结合……

Education

教育

JoVE Core

Molecular Biology

分子生物学

Unit 1

第一单元

Gene Expression

基因表达

KEY TERMS AND CONCEPTS

关键术语与概念

how eukaryotic gene repressors work

Eukaryotic gene repressors help turn specific genes off when the cell needs to control growth, development, or other biochemical processes. These DNA-binding proteins regulate gene expression in eukaryotes. Their presence at the right time and place can be triggered by hormones and signals from other cells.

Most transcription inhibitors have two main parts. One part binds DNA, and the other is a repressor domain, which helps shut down transcription. Repressor domains can connect with basal transcription regulators, activators, co-activators, and co-repressors.

These repression domains are often grouped by their amino acids, such as alanine-rich, glutamine-rich, and proline-rich domains. They can also be described as acidic or basic, and as hydrophilic or hydrophobic. Different repressor domains can often be swapped onto the same DNA-binding domain.

Eukaryotic transcription inhibitors act through three main mechanisms: inhibiting DNA binding, blocking activation, and gene silencing. Inhibiting DNA binding stops an activator from attaching to a promoter or enhancer, or it prevents the transcription initiation complex from binding the transcription start site or the TATA box. This can happen when the inhibitor binds the regulatory site or start site, or when its inhibitory domain interacts with activators, co-activators, or other transcription machinery proteins.

One example is NF-E in humans. It binds the CCAAT box of the fetal gamma-globin gene and blocks the activator CP1 from binding. Blocking activation works differently. The inhibitor can bind next to a promoter or enhancer, as in c-myc regulation, where myc-PRF binds beside the promoter. It can also bind to an activator already attached to DNA. In yeast, GAL80 binds GAL4 when GAL4 is bound to the promoter.

Gene silencing happens when the inhibitor locks or disrupts the transcription initiation complex. It does this by binding both a protein in the machinery and a DNA site near the transcription start site, which anchors the complex. In yeast, the alpha-2 inhibitor works this way to turn off mating type a-specific genes. It binds as a dimer to the activator GRM and to DNA sequences beside the GRM binding site.

How Eukaryotic Gene Repressors Work

cell specific gene expression

How Cells Switch Genes On and Off

Cells switch genes on and off to make different proteins for different jobs. In multicellular organisms, many cell types are built from the same DNA, but they do not use the same genes in the same way. This difference in gene expression helps explain why cells can look and act so differently. Liver cells are a clear example. They help detoxify blood, make bile to help digest fats, and produce proteins needed for metabolism. To do these jobs, liver cells must express a specific set of genes.

regulation of expression occurs at multiple steps

regulation-of-expression-occurs-at-multiple-steps

How Cells Control Gene Expression

Cells control gene expression at several points between DNA and protein. The most common control point is transcription. At this stage, proteins bind to short regulatory DNA sequences and can either increase or reduce transcription of the linked gene. After transcription, a precursor mRNA is made. This pre-mRNA contains exons, which code for protein, and introns, which do not. It must be processed before translation, and splicing removes the introns and joins the exons. Cells can also regulate...

cis-regulatory sequences

How Cis-Regulatory DNA Controls Transcription

Cis-regulatory sequences are short, non-coding DNA segments that control gene transcription. They sit on the same chromosome as the genes they regulate and act as binding sites for transcriptional regulators. In eukaryotes, these proteins help control gene expression patterns in different cell types. These DNA sequences can be close to a gene or thousands of bases away. When they are far from the gene in the DNA sequence, they are often brought close together in space because chromosomes are...

cooperative binding of transcription regulators

cooperative-binding-of-transcription-regulators

How Transcription Factors Bind DNA

Transcriptional regulators bind to cis-regulatory DNA sequences to control gene transcription. These DNA sequences are very short, usually fewer than ten nucleotide pairs long. Because they are so short, the same sequence can appear by chance in many places across the genome. Some regulators can also bind to groups of similar sequences. That raises the chance of random binding even more. To lower this risk, transcription regulators often form dimers, which are pairs of proteins that bind a DNA...

prokaryotic transcriptional activators and repressors

prokaryotic-transcriptional-activators-and-repressors

Operon Control by Activators and Repressors

Operon control in prokaryotes depends on activators and repressors. Prokaryotic genes are often arranged in groups, not one by one like in eukaryotes. Genes that help carry out the same biochemical process are placed together with their regulatory elements. This group is called an operon, and it is transcribed into a single polycistronic mRNA strand. Activators and repressors are DNA-binding proteins that control transcription in an operon. Activators bind near the promoter, which is the site...

operons

Operons in Bacterial Gene Control

Operons help bacteria control groups of genes at the same time. An operon is a set of genes that are regulated together and can be turned on or off as a unit. This shared control helps bacteria respond quickly to changes in their environment. In many operons, a promoter gives RNA polymerase a place to bind and start transcription. The operon also includes a regulatory region that helps control whether the genes are expressed. When conditions change, the cell can use this setup to manage gene...

the eukaryotic promoter region

Eukaryotic Promoter Motifs and Gene Control

The eukaryotic promoter region is a stretch of DNA located upstream of a gene. It includes an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. These DNA signals help control when transcription begins. The promoter can be divided into proximal and distal regions. The proximal promoter lies close to the gene and includes cis-regulatory sequences and the core promoter. The core promoter is the RNA polymerase binding site, and it is usually found...

co-activators and co-repressors

Chromatin Control in Gene Transcription

Chromatin control plays a major role in gene transcription in eukaryotes. Gene expression is regulated by several proteins that work together at a gene regulatory site. Some of these proteins bind directly to specific DNA sequences, while co-regulators attach to those regulators but do not bind DNA on their own. Co-regulators can act as co-activators or co-repressors, depending on the complex they join. One co-regulator may even switch roles in different settings. For example, the...

eukaryotic transcription activators

How Transcription Activators Turn Genes On

Transcription activators are proteins that help turn genes on by promoting transcription from DNA to RNA. They often have two parts. One part binds to DNA, and the other part activates transcription. In some proteins, such as the glucocorticoid receptor and MyoD, one domain can do both jobs. The DNA-binding part recognizes specific regulatory sequences on the DNA. These binding domains are grouped into families based on their structure. Common examples include the leucine zipper, zinc finger,...

eukaryotic transcription inhibitors

Eukaryotic gene repressors help turn specific genes off when the cell needs to control growth, development, or other biochemical processes. These DNA-binding proteins regulate gene expression in eukaryotes. Their presence at the right time and place can be triggered by hormones and signals from other cells. Most transcription inhibitors have two main parts. One part binds DNA, and the other is a repressor domain, which helps shut down transcription. Repressor domains can connect with basal...

combinatorial gene control

Gene Expression by Transcription Factor Combinations

Gene expression can depend on combinations of transcription factors working together. In combinatorial gene control, several transcription factors act in a coordinated way to regulate a single gene. If one or more of these factors are missing, the level of gene expression or repression can change a lot. This kind of control helps explain how a relatively small number of transcription factors can regulate a very large number of genes. More than 30,000 genes are controlled by about 2,000 to...

induced pluripotent stem cells

Reprogramming Cells into Stem Cells

Induced pluripotent stem cells are created by reprogramming mature cells back into a stem-cell state. This process shows that specialized cells can be changed into cells with broader developmental potential. The topic is important in biology because it links cell identity, gene control, and stem cell research. These cells begin as ordinary body cells and are pushed to de-differentiate, or lose their specialized features. After reprogramming, they behave like pluripotent stem cells, which means...

master transcription regulators

MEF2C and Gene Control Cascades

MEF2C is a master transcription regulator that controls gene expression in coordinated cascades. These regulators are proteins that manage the activity of multiple genes that often work together to produce a complex outcome. When a master transcription regulator is activated, it can start a chain of transcriptional activation that supports that outcome. Master transcription regulators can act in two main ways. They may bind directly to the regulatory sequences of several genes involved in a...

epigenetic regulation

DNA Methylation and Histone Changes

Epigenetic regulation controls gene activity without changing the DNA sequence. It helps determine when genes are turned on or off in a cell. Two major epigenetic mechanisms are DNA methylation and histone modification. DNA methylation adds chemical groups to DNA, while histone changes affect how tightly DNA is packed around histone proteins. These changes can make genes easier or harder to use. In high school biology, epigenetic regulation is important for understanding how cells with the...

genomic imprinting and inheritance

Genomic Imprinting in Human Disease

Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way. In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are...

key terms and concepts

Learn how eukaryotic gene repressors control transcription through DNA binding, blocking activation, and gene silencing, with clear examples from humans and yeast.

How Eukaryotic Gene Repressors Work | JoVE K12

molecular biology

JoVE Core 分子生物学通过清晰简洁的动画视频课程展示了细胞的分子过程。此外，在科学家在行动的视频中，这些概念的应用是通过现代实验室中的真实实验演示的。

How Eukaryotic Gene Repressors Work

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