Name: histone marks and gene control
Uploaded: 2020-11-23T11:47:35.000Z
Duration: 2 min 32 s
Channel: JoVE

K12 Standards

Louisiana Student Standards for Science

High School

Life Sciences

heredity-inheritance-and-variation-of-traits

Heredity: Inheritance And Variation Of Traits

HS-LS3-1

Histone Modification

A nucleosome contains a protein core that is made up of four histone core proteins: H2A, H2B, H3, and H4.
In addition to these four standard core histones, eukaryotes also possess a few variants of each histone, with the exception of H4.&#160;
The amino-terminal tails of the core standard and variant core histones protrude from the nucleosomes and are highly unstructured and mobile.
These tails, comprising of about 30 amino acids, are subjected to several forms of covalent modifications such as the acetylation of lysines, phosphorylation of serines, and mono-, di-, or tri-methylation of lysines.&#160;
The reactions that lead to these modifications are catalyzed by different enzymes such as methyltransferases, acetylases, kinases. These groups of enzymes are collectively referred to as the &#8216;writers.&#8217;&#160;
The reactions that catalyze the removal of these chemical groups are catalyzed by enzymes such as demethylases, deacetylases, and phosphatases. These enzymes are collectively referred to as the &#8216;erasers.&#8217;
Amongst the numerous possible combinations of different histone variants and amino-terminal end modifications, only certain coordinated sets are known to occur. Some of these combined sets of m

histone modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form &#8220;histone codes&#8221; that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase, removes the acetyl group from acetylated histones. The lysine amino acids at position 4 and 9 of N-terminal histone tail are often acetylated and deacetylated. Acetylation increases the negative charge of histones. This weakens the DNA-histone interaction resulting in loosening of chromatin and increased access to DNA. For example, in the erythroid cells, beta-globin gene is associated with acetylated histones that increase its expression. In non-erythroid cells where the gene is inactive, it is found to be associated with nonacetylated histones.
Methylation
The histone tails at the lysine 9 position of histone H3 can be di- or tri-methylated by enzyme histone methyltransferase. This methylation can initiate the binding of nonhistone proteins and increase chromatin compaction. Methylation increases the positive charge on the histones, resulting in increased affinity between negatively charged DNA and histones and higher chromatin compaction. Repressed chromatin, also known as heterochromatin, is highly methylated.
Summary table of histone modifications and their effect on gene expression
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Histone modification</td>
			<td>Effect on gene expression</td>
		</tr>
		<tr>
			<td>Acetylated lysine</td>
			<td>Activation</td>
		</tr>
		<tr>
			<td>Hypoacetylated lysine</td>
			<td>Repression</td>
		</tr>
		<tr>
			<td>Phosphorylated serine/threonine</td>
			<td>Activation</td>
		</tr>
		<tr>
			<td>Methylated arginine</td>
			<td>Activation</td>
		</tr>
		<tr>
			<td>Methylated lysine</td>
			<td>Repression</td>
		</tr>
		<tr>
			<td>Ubiquitinylated lysine</td>
			<td>Activation/Repression</td>
		</tr>
	</tbody>
</table>
The histone codes or modifications are epigenetically inherited, meaning these modifications are not genetically coded. Hence, these modifications are faithfully passed on to the next cell during each cell division as an epigenetic memory.

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational ...

Education

JoVE Core

Molecular Biology

Unit 1

DNA and Chromosome Structure

KEY TERMS AND CONCEPTS

histone marks and gene control

Histone marks help control how tightly DNA is packed and how genes are turned on or off. Histone proteins have a flexible N-terminal tail that extends out from the nucleosome. These tails can be modified after the protein is made. Common modifications include acetylation, methylation, phosphorylation, and ubiquitination.

Different combinations of these changes create a histone code. This code influences chromatin folding and tissue-specific gene expression. In other words, the same DNA can behave differently in different cell types because the histone marks are not the same.

Acetylation is added by histone acetyltransferase, and histone deacetylase removes it. Lysine residues at positions 4 and 9 on the N-terminal histone tail are often acetylated or deacetylated. Acetylation increases the negative charge of histones. This weakens the DNA-histone interaction, loosens chromatin, and gives DNA better access. In erythroid cells, the beta-globin gene is linked to acetylated histones and shows higher expression. In non-erythroid cells, where the gene is inactive, it is linked to nonacetylated histones.

Methylation has the opposite effect in many cases. Histone methyltransferase can add two or three methyl groups to lysine 9 on histone H3. This can help nonhistone proteins bind and can increase chromatin compaction. Methylation also increases the positive charge on histones, which strengthens their attraction to negatively charged DNA. Repressed chromatin, or heterochromatin, is highly methylated.

Other histone marks also affect gene expression. Acetylated lysine and phosphorylated serine or threonine are linked with activation. Methylated arginine is also linked with activation. Methylated lysine is linked with repression, while ubiquitinylated lysine can support activation or repression. These histone codes are epigenetically inherited, which means they are not written in the DNA sequence itself. They are passed to daughter cells during cell division as epigenetic memory.

Histone Marks and Gene Control

dna packaging

DNA Packaging in Chromosomes

DNA packaging in chromosomes helps cells fit long DNA molecules into a compact space. The DNA must be organized so it can be stored and used by the cell. This packaging also supports chromosome structure. In eukaryotic cells, DNA wraps around histone proteins. Histones help form chromatin, which is the DNA-protein material that makes up chromosomes. This arrangement packs DNA more tightly while still keeping it organized. The way DNA is packaged affects how a cell manages its genetic material.

dna as a genetic template

DNA Replication Proved by Meselson-Stahl

DNA replication was confirmed by the Meselson and Stahl experiment, which tested how DNA copies itself. The experiment also connects to the Watson-Crick model of DNA, first proposed in 1952. That model was built from X-ray crystallography work by Rosalind Franklin and Maurice Wilkins, and Watson, Crick, and Wilkins later shared the 1962 Nobel Prize in Physiology or Medicine. Franklin was not included, and that decision remains debated. The Watson-Crick model describes DNA as two strands of...

organization of genes

Genes on Chromosomes: DNA Organization

Genes are organized within DNA and packed into chromosomes. This structure helps keep genetic information arranged and readable inside the cell. A gene is a segment of DNA that carries instructions for a specific trait or product. In many genes, the coding sequence is broken into exons, which are the parts that remain in the final message, and introns, which are removed before the message is used. The order of these parts is part of how genes are organized. Genes also include regulatory...

chromosome structure

Chromosome Ends, Centers, and Replication

A functional eukaryotic chromosome needs three key parts: a centromere, telomeres, and many origins of replication. These regions help the chromosome stay organized, copy its DNA, and move correctly during cell division. The centromere is a DNA sequence that holds sister chromatids together. After the chromosome is replicated, this region is where kinetochores are built. Kinetochores are protein complexes that bind spindle microtubules, which help move chromosomes within the cell during...

chromosome replication

Origins of Replication in Chromosomes

Chromosome replication starts at many origins of replication during the S phase of the cell cycle. Each chromosome copies its DNA at the same time. The process also includes the histone and non-histone proteins attached to the DNA. By the time the cell reaches M phase and is ready to divide, its chromosomal mass has effectively doubled. Replication begins at nucleotide sequences called origins of replication. These sites work with specialized initiator proteins that start DNA separation and...

the nucleosome

How DNA Is Packed into Nucleosomes

DNA in a human cell is almost 2 m long, yet it fits inside a nucleus that is only a few microns wide. To make this possible, DNA is packed into several higher levels of compaction. The most compact form is a chromosome, which can be seen under a microscope in a dividing cell. A key step in this packing process is the nucleosome. In a nucleosome, DNA winds twice around a histone core made of 8 histone proteins. This DNA and histone protein complex is the fundamental and functional unit of DNA...

the nucleosome core particle

Histone Tail Modifications in Nucleosomes

Nucleosomes are DNA wrapped around a histone core. The core is an octamer, or eight-protein complex, made of two copies each of H2A, H2B, H3, and H4. This DNA-histone structure helps package DNA while still keeping it organized inside the cell. Nucleosomes have to balance two opposite jobs. They protect delicate DNA from physical damage and help create a higher level of compaction. At the same time, they must let polymerase enzymes reach the DNA for replication and transcription. Nucleosomes...

nucleosome remodeling

How Chromatin Opens for DNA Access

Chromatin must open at the right time so proteins can reach DNA. Nucleosomes, the basic units of chromatin compaction, wrap DNA tightly around a histone core. This packing makes DNA less accessible to proteins such as DNA polymerase and RNA polymerase. Eukaryotic cells use ATP-dependent nucleosome remodeling enzymes to solve this problem. These enzymes bind to histones and the wrapped DNA. They can shift nucleosomes along DNA, a process called nucleosome sliding, or replace part or all of the...

chromatin packaging

DNA Packing Inside the Nucleus

DNA packing inside the nucleus depends on chromatin and histones. Each human somatic cell contains about 6 billion base-pairs of DNA. Because each base-pair is 0.34 nm long, a diploid cell holds about 2 meters of DNA. That long strand must fit inside a nucleus that is only 10 to 20 microns wide. Chromatin is the compact DNA-protein complex formed when the DNA double helix combines with specialized DNA-binding proteins called histones. Chromatin is then packed even further into higher-order...

karyotyping

Chromosome Pairing and Karyotypes

Chromosome pairing and karyotypes help scientists study the number and structure of chromosomes in a cell. A karyotype is a visual display of chromosomes arranged in matching pairs. It can reveal large-scale changes that affect chromosome shape or count. To make a karyotype, chromosomes are first collected when they are most condensed and easiest to see. They are then stained and photographed so the pairs can be organized. The finished image gives a clear view of the full chromosome set in one...

position-effect variegation

Chromatin Spreading and Gene Silencing

Chromatin spreading can silence a gene when it moves near heterochromatin. This effect is called position-effect variegation, or PEV. It happens because the gene’s location changes, not because the gene itself changes. Emil Heitz first noticed that some chromatin in moss nuclei spread out during interphase, while other regions stayed compact. He named the open form euchromatin and the compact form heterochromatin. He suggested that heterochromatin marked a part of the genome that was...

Histone marks help control how tightly DNA is packed and how genes are turned on or off. Histone proteins have a flexible N-terminal tail that extends out from the nucleosome. These tails can be modified after the protein is made. Common modifications include acetylation, methylation, phosphorylation, and ubiquitination. Different combinations of these changes create a histone code. This code influences chromatin folding and tissue-specific gene expression. In other words, the same DNA can...

spreading of chromatin modifications

Histone Marks and Chromatin Boundaries

Histone marks help control how tightly DNA is packed in chromatin. These post-translational modifications, or PTMs, happen on histone proteins in nucleosomes and can increase or decrease access to DNA. Common PTMs include methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone marks carry specific meaning for the cell. For that reason, they are often called the histone code. The protein complex that helps place and read...

lampbrush chromosomes

Lampbrush Chromosomes in Oocyte Meiosis

Lampbrush chromosomes are large chromosomes found in oocytes during meiosis. They are best known from lower vertebrates, invertebrates, and birds. Their unusual shape and size make them a useful model for studying chromosome structure and gene activity. Flemming first observed lampbrush chromosomes in salamander eggs in 1882. Later, in 1892, Rückert saw them in shark egg cells and gave them their name. He chose the term because they looked like the brushes used to clean kerosene lamps. These...

polytene chromosomes

Polytene Chromosomes in Salivary Glands

Polytene chromosomes are giant interphase chromosomes made of many DNA strands aligned side by side. They were first described by Balbiani in 1881. They are often called salivary gland chromosomes because they are regularly seen in salivary gland cells, especially in Drosophila. These chromosomes are found in insects of the order Diptera and Collembola. They also appear in certain organs of mammals and in synergids and antipodes of flowering plants. In larvae of Chironomus plumosus, they were...

histone variants at the centromere

CENP-A and Centromere Identity

CENP-A is a specialized histone H3 variant found in centromeric chromatin. It has about 60% similarity to canonical histone H3. This histone variant helps build the kinetochore, the protein structure that links chromosomes to microtubules during cell division. CENP-A is also thought to act as an epigenetic mark. An epigenetic mark is a signal that helps cells keep centromere identity without changing the DNA sequence. The centromere-targeting process depends on the CENP-A targeting domain, or...

inheritance of chromatin structures

Epigenetic Memory in Chromatin

Epigenetic memory in chromatin helps cells keep their identity without changing the DNA sequence. Epigenetics is the study of inherited changes in cell phenotype that do not alter DNA. This kind of memory helps maintain cell lineage, position-effect variegation, dosage compensation, and chromatin structures such as telomeres and centromeres. Centromeres are a clear example of this process. Their structure and location on chromosomes can be inherited epigenetically. Centromere function is not...

euchromatin

Euchromatin and DNA Packaging

Euchromatin is the less compact form of chromatin. Chromatin can be studied by staining DNA with specific dyes, because dense regions take up more dye and appear darker under the microscope. Lighter-staining areas are less compact, and euchromatin is one of these regions. This open chromatin state is linked to histone changes. Histone H3 in euchromatin is extensively acetylated on lysine 9. In promoter regions, histones can also carry methylated lysine 4 and phosphorylation at position 10.

chromatin position affects gene expression

chromatin-position-affects-gene-expression

Chromatin Folding Shapes Gene Activity

Chromatin folding inside the nucleus shapes gene activity in eukaryotic cells. Chromatin is the large complex of DNA and proteins packed into the nucleus. How it is arranged affects how easily genetic information can be reached. In general, the nucleus periphery is linked with lower transcription, while the cell interior is linked with more active transcription. Gene promoters are often kept physically separate from regulatory DNA elements such as enhancers. To turn on gene expression, these...

heterochromatin

Heterochromatin Staining and Chromatin Packing

Heterochromatin is the tightly packed form of chromatin, and it can be seen by staining DNA with specific dyes. Under the microscope, these dense regions take up more dye than less compact chromatin. Heterochromatin is usually divided into constitutive heterochromatin and facultative heterochromatin. Constitutive heterochromatin is a highly compact part of chromatin. It is mostly found at centromeres and telomeres. In this form, the amino acid at position 9 on the histone H3 tail is di- or...

key terms and concepts

Explore how acetylation, methylation, and other histone marks change chromatin packing and affect gene expression in high school biology.

Histone Marks and Gene Control | JoVE K12

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JoVE Core Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

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Biology

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From Molecules to Organisms: Structures and Processes

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Next Generation Science Standards

Life Science

Heredity: Inheritance and Variation of Traits

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South Carolina College and Career Ready Science Standards

B-LS3-1.

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New York State Science Learning Standards

Inheritance and Variation of Traits

HS-LS3-1.

What are Cells?

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Cytoplasm

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The Nucleus

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Chromosome Replication

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The Nucleosome

DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside ...

The Nucleosome Core Particle

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Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA ...

Chromatin Packaging

Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 ...

Karyotyping

Spreading of Chromatin Modifications

The histone&#160;proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are ...

Histone Variants at the Centromere

Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as &#8220;mutant&#8221; forms that ...

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell&#39;s phenotype without changing the DNA sequences. It provides a form of memory for the ...

Euchromatin

The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions ...

Heterochromatin

Chromatin Position Affects Gene Expression

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Punnett Squares

Monohybrid Crosses

Dihybrid Crosses

Trihybrid Crosses

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Law of Independent Assortment

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Pedigree Analysis

Multiple Allele Traits

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Lethal Alleles

Agouti: A Lethal Allele
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Polygenic Traits

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Background and Environment Affect Phenotype

Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as ...

Formulate, refine, and evaluate questions to clarify relationships about the role of DNA and chromosomes in coding the instructions for characteristic traits passed from parents to offspring. Emphasis should be on traits including completely dominant, codominant, incompletely dominant, and sex-linked traits (e.g., pedigrees, karyotypes, genetic disorders, Punnett squares). Examples do not need to include dihybrid crosses.

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X-linked Traits

Sex Linked Disorders

Dosage Compensation

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X-inactivation

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Meiosis I

Meiosis II

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Nondisjunction

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Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors. Emphasis is on using data to support arguments for the way variation occurs. Claims should not include the phases of meiosis or the biochemical mechanisms of specific steps in the process.

HS-LS3-2

Mutations

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Base-pairing and DNA Repair

The DNA Replication Fork

Lagging Strand Synthesis

The Replisome

Proofreading

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Replication in Eukaryotes

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HS-LS3-3

Histone Marks and Gene Control

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