Name: chromatin control in gene transcription
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 2 min 4 s
Channel: JoVE

转录受到调节 通过激活剂和阻遏剂-与DNA结合的蛋白质。在真核生物中，这些 调节蛋白 经常需要额外的 称为共调蛋白的蛋白 正常运行。这些核心调节者绑定 激活或抑制 复合体。但是，它们无法识别 顺式调控序列 因为它们无法束缚 直接与DNA结合。转录 调节剂结合 协助调节顺序 在共同调节子 联合之前。调节子和共同调节子 经常无法形成稳定 复合物，除非 调节子与DNA结合。在某些情况下，RNA分子也 充当支架 将所有蛋白质复合 在一起。其中一些 合调剂是酶 可以调节 基因表达，如组蛋白 乙酰转移酶 和脱乙酰基酶。乙酰转移酶 是共同激活者 以乙酰转移 组蛋白组导引 使DNA松动 并促进转录。脱乙酰基酶是核心加压因子 去除乙酰基 导致包装紧密 组蛋白周围的DNA 并防止转录。例如，共同调节子SMRT联合 甲状腺 激素受体 在阳性激素 响应元素 并充当 抑制基础转录。当激素结合时 对受体 SMRT分离 和一个辅助激活剂 结合以激活转录。但是，当绑定到相同 荷尔蒙阴性受体 响应元素，SMRT 激活转录 在缺激素的情况下 从而 充当共同激活者。

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	<li>李，JW，张，J.，李，Y.C.，纳，S.Y.和李，S. K.（2000）。剖析核受体作用的分子机制:转录共激活因子和辅阻遏物。实验与分子医学，32（2），53-60。</li>
	<li>Gao， Z.， Chiao， P.， Zhang， X.， Zhang， X.， Lazar， MA， Seto， E.， ...& Ye， J. （2005）.IκBα 基因启动子中 NF-κB 的共激活因子和辅抑制因子。生物化学杂志， 280（22）， 21091-21098.</li>
	<li>Purcell， D. J.， Jeong， K. W.， Bittencourt， D.， Gerke， D. S.， & Stallcup， M. R. （2011）.组蛋白甲基转移酶 G9a 在转录调控中共激活因子与辅阻遏蛋白功能的不同机制。生物化学杂志， 286（49）， 41963-41971。</li>
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共激活因子和共抑制因子

Co-activators and Co-repressors

基因转录是通过在基因调控位点形成复合物的几种蛋白的协同作用来调控的。 这是在真核生物中观察到的，其中基因表达的调控是一个复杂的过程。 真核生物中的调控蛋白大致可分为两类：直接与特定 DNA 序列结合的调控蛋白和与调控蛋白相关但不能直接与 DNA 结合的辅助调控蛋白。 这些共调控因子根据其功能进一步分为共激活因子或共抑制因子。

一个共调控因子可以根据其在相关复合物中的作用而兼具共激活或共抑制功能。例如，转录辅阻遏物 G9a 与其他辅激活因子（例如 GRIP1 和 CARM1）一起参与类固醇激素受体基因表达的激活。 该蛋白的不同结构域执行这些不同的功能。 除了在复合物中的作用外，这些调控因子还具有酶活性，可以通过染色质结构的重塑来帮助调控基因表达。

组蛋白乙酰转移酶和组蛋白去甲基酶作为共激活因子起作用； 然而，它们首先需要通过转录激活因子定位到调控位点才能执行这些功能。 组蛋白乙酰转移酶可以乙酰化组蛋白尾部的赖氨酸残基。 乙酰化使染色质解卷并促进基因表达。 另一方面，组蛋白脱乙酰酶和组蛋白甲基转移酶充当共阻遏物。 这两种修饰都会导致染色质结构收紧，从而阻止基因表达。

基因转录受到多个蛋白质协同作用的调控，这些蛋白质在基因调控位点处形成复合物。这一现象在……中被观察到。

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

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 transcriptional co-repressor G9a helps activate a steroid hormone receptor gene with co-activators such as GRIP1 and CARM1. Different protein domains help carry out these different jobs.

Many of these regulators also have enzyme activity that changes chromatin structure. Histone acetyltransferases and histone demethylases act as co-activators, but they must first be brought to the regulatory site by a transcription activator. Histone acetyltransferases add acetyl groups to lysine residues on histone tails, which loosens chromatin and supports gene expression.

Other enzymes act as co-repressors. Histone deacetylases and histone methyltransferases tighten chromatin structure and reduce gene expression. These chromatin changes help explain how co-regulators can either turn genes on or keep them off.

Chromatin Control in Gene Transcription

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 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

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...

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 co-regulators change chromatin to turn genes on or off, including histone acetylation, deacetylation, and methylation in eukaryotes.

Chromatin Control in Gene Transcription | 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。

Chromatin Control in Gene Transcription

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