Name: dna methylation and histone changes
Uploaded: 2020-11-23T11:47:38.000Z
Duration: 1 min 46 s
Channel: JoVE

후성 유전학적 조절이란유전자 배열의 변화 없이유전될 수 있는 유전자 발현의 변화를 뜻합니다이는 정상적인 발달 과정 중에도 일어나고식단이나 독성 물질에의 노출,그리고 스트레스 등에 인해서도 발생할 수 있습니다후성 유전학적 조절은세 가지 과정을 통해 발생합니다DNA 메틸화, 히스톤 변이, 그리고RNA 기반 과정이 그것입니다DNA 메틸화 중에 CH3 그룹인 메틸은특정 염기에 추가가 됩니다이 과정은 전사 인자와 같은조절 단백질의 기능을 바꾸어DNA에 결합하게 되고, 이럴 경우 보통 유전자가전사되는 것을 막습니다히스톤 변이는메틸이나 아세틸 그룹과 같은 화학 그룹을염색질을 형성하기 위해 DNA가 감싸고 있는히스톤 단백질에 추가하는 과정을 뜻합니다이러한 변이는염색질이 접히거나 열리는 정도에영향을 주어더 쉽게 전사가 되거나전사를 막게끔 압축 하게끔 하는 역할을 합니다다양한 종류의 RNA는 또한 염색질 구조를 바꿀 수 있는마이크로 RNA와 소간섭 RNA와 같은후성 효과를 가집니다그리고 메틸화 될 수 있는 전령 RNA는유전자 번역을 바꿀 수도 있죠어떤 방법으로든,이런 변이는 딸세포로 전달이 되고때때로 다음 세대로까지전달이 되어게놈에 변형을 야기하지 않고장기적인 표현형의 변형을 발생시킬 수 있습니다

와인홀드, 밥. "후성유전학: 변화의 과학." Environmental Health Perspectives 114, no. 3 (March 2006): A160–67. [<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1392256/" target="__blank">출처</a>]

Gudsnuk, Kathryn, and Frances A. Champagne. "스트레스와 사회 환경의 후성유전학적 영향." ILAR Journal 53, no. 3–4 (December 2012): 279–88. [<a href="https://doi.org/10.1093/ilar.53.3-4.279" target="__blank">소스</a>]

Simmons, Danielle "후성 유전 학적 영향과 질병." Nature Education 1 no. 1 (2008) : 6  [<a href = "https://www.nature.com/scitable/topicpage/epigenetic-influences-and-disease-895" target ="__blank">출처</a>]

Lim, Derek H. K., and Eamonn R. Maher. "DNA 메틸화: 유전자 발현의 후성유전학적 조절의 한 형태." The Obstetrician & Gynaecologist 12, no. 1 (2010): 37–42. [<a href="https://doi.org/10.1576/toag.12.1.037.27556" target="__blank">출처</a>]

후성유전적 조절

Epigenetic Regulation

후성유전적(epigenetics; 후생유전) 기작은 건강한 발달에 중요한 역할을 합니다. 반대로 정확하게 조절된 후성유전적 기작은 암과 같은 질병에서 교란됩니다.
 
 대부분의 포유류 암컷은 2개의 X 염색체(XX)를 가지고 있지만, 수컷은 X 염색체와 Y 염색체(XY)를 가지고 있습니다. X 염색체는 Y 염색체보다 훨씬 더 많은 유전자를 가지고 있습니다. 따라서, X 염색체 관련 유전자의 과잉발현을 막기 위해 여성의 X 염색체 둘 중 하나는 초기 발달 중에 무작위로 침묵합니다. X 염색체 비활성화(X-chromosome inactivation)라고 불리는 이 과정은 DNA 메틸화(methylation)에 의해 조절됩니다. 과학자들은 비활성 X 염색체의 유전자 프로모터 부위(promoter site; 촉진자 부위)가 활성 X 염색체에 있는 같은 부위보다 더 많이 메틸화되어있는 것을 발견했습니다. DNA 메틸화는 전사 인자가 프로모터 부위에 부착하는 것을 방지하여 유전자 전사(transcription)를 억제합니다.
 
 비정상적인 DNA 메틸화는 암에서 중요한 역할을 합니다. 대부분의 유전자 프로모터 부위는 인산기(phosphate group)에 의해 연결된 사이토신(cytosine; 시토신)과 구아닌(guanine) 뉴클레오타이드(nucleotide) 구간을 포함합니다. 이 지역들을 CpG 섬(CpG island)이라고 부릅니다. 건강한 세포의 CpG 섬은 메틸화되지 않습니다. 그러나 암세포에선 종양 억제 유전자(tumor suppressor gene)나 세포 주기 조절자(cell cycle regulator)의 프로모터 부위에 있는 CpG 섬들이 과도하게 메틸화됩니다. 메틸화는 이런 유전자의 발현을 중단 시켜 암세포가 빠르고 통제 불가능하게 분열하게 만듭니다.

후성유전학적 메커니즘은 건강한 발달에 필수적인 역할을 합니다. 반대로, 정확하게 조절되는 후성유전학적 메커니즘은 다음과 같은 질병에서 방해를 받습니다.

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 same DNA can still act differently. It also shows how gene expression can be controlled by chemical marks on DNA and chromatin, the DNA-protein complex in the nucleus.

DNA Methylation and Histone Changes

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

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

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 epigenetic regulation controls gene activity through DNA methylation and histone modification, and why these changes matter in cells.

DNA Methylation and Histone Changes | JoVE K12

molecular biology

JoVE Core 분자생물학은 명확하고 간결한 애니메이션을 통해 분자 단계에서 일어나는 세포 과정을 설명합니다.또한, 과학자가 직접 실험을 진행하는 실사 영상을 통해 분자생물학 개념의 응용 사례를 보여줍니다.

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DNA Methylation and Histone Changes

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