Name: chromatin spreading and gene silencing
Uploaded: 2020-11-23T11:47:35.000Z
Duration: 2 min 32 s
Channel: JoVE

K12 Standards

Next Generation Science Standards

High School

Life Science

heredity-inheritance-and-variation-of-traits

Heredity: Inheritance and Variation of Traits

HS-LS3-1

Position-effect Variegation

In a eukaryotic cell, DNA associates with various proteins to form a tightly packed, highly condensed structure called chromatin. Chromatin is divided into two types, depending upon the level of compaction.
Heterochromatin, concentrated in the centromeres and telomeres, is highly condensed, gene-poor, and infrequently transcribed into RNA.&#160;
In contrast, euchromatin, which constitutes a majority of the chromosomal material, is less condensed, gene-rich, and actively transcribed.&#160;
Heterochromatin and euchromatin are separated by barrier DNA sequences. These sequences prevent the spread of heterochromatin and maintain stable gene expression patterns.&#160;
During DNA rearrangement events, such as transposition, a piece of euchromatin can be translocated near a heterochromatin region without any adjacent DNA barrier sequences.
In such events, genes that are typically active are &#8216;silenced&#8217; or &#8216;inactivated.&#8217; This phenomenon is known as the &#8216;position effect.&#8217;&#160;
For example, in Drosophila, red eye color is encoded by the &#8216;white&#8217; gene. Occasionally, &#8216;white&#8217; is moved near a heterochromatin region without any DNA barrier sequences in between.&#160;
When flies inherit this genotype, during their early em

position-effect variegation

In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
Difference between euchromatin and heterochromatin
Euchromatin is a lightly stained, gene-rich, and loosely-bound chromatin region. It is usually dispersed in the nucleus. The histones of euchromatin are extensively acetylated, which allows loose chromatin compaction.
In contrast, heterochromatin is a darkly stained, repeat-rich, gene-poor, and compact chromatin. It is mostly seen at the nuclear periphery, often as clumps. The histones of heterochromatin are methylated, which enables a compact chromatin structure.
Position-effect variegation
Chromosomal rearrangements may position euchromatin genes next to heterochromatin. Such gene rearrangements can result in gene silencing by virtue of being placed near heterochromatin, rather than a change in the gene itself. This phenomenon is called &#34;position-effect variegation (PEV).&#34; Hence, the juxtaposed gene becomes silent in some cells where it is normally active, resulting in a variegated phenotype. The phenomenon of PEV is well studied in Drosophila.
The formation of heterochromatin depends on the histone H3 methylation followed by the association with nonhistone proteins such as Heterochromatin Protein 1 or HP1. Usually, heterochromatin and euchromatin are separated by a buffer region with many repeat-rich regions. PEV indicates that heterochromatin, once formed, can spread beyond the buffer region into the adjoining chromatin. In humans, HUSH complex methylates histones and contributes to the spreading of heterochromatin and hence, position effect variegation.

In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread ...

Education

JoVE Core

Molecular Biology

Unit 1

DNA and Chromosome Structure

KEY TERMS AND CONCEPTS

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 functionally inactive.

Euchromatin is lightly stained, gene-rich, and loosely packed. It is usually spread throughout the nucleus. Its histones are heavily acetylated, which helps keep the chromatin open. Heterochromatin is darkly stained, repeat-rich, and gene-poor. It is tightly packed, often sits near the nuclear edge, and appears as clumps. Its histones are methylated, which supports the compact structure.

When a chromosome rearrangement places an active euchromatin gene next to heterochromatin, the gene may be switched off in some cells. This creates a variegated phenotype, meaning the trait appears in patches. PEV is well studied in Drosophila. Heterochromatin formation depends on histone H3 methylation and nonhistone proteins such as Heterochromatin Protein 1, or HP1. In many cases, euchromatin and heterochromatin are separated by a repeat-rich buffer region, but PEV shows that heterochromatin can spread past that boundary. In humans, the HUSH complex also methylates histones and helps heterochromatin spread, which can contribute to PEV.

Chromatin Spreading and Gene Silencing

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...

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 modification

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...

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

Learn how heterochromatin can spread, silence nearby genes, and cause position-effect variegation in Drosophila and humans through chromatin changes.

Chromatin Spreading and Gene Silencing | JoVE K12

molecular biology

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.

south-carolina-college-and-career-ready-science-standards

South Carolina College and Career Ready Science Standards

Biology

B-LS3-1.

new-york-state-science-learning-standards

New York State Science Learning Standards

Inheritance and Variation of Traits

HS-LS3-1.

DNA as a Genetic Template

Structure of a Gene

A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the ...

DNA Packaging

Organization of Genes

Chromosome Structure

A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
The centromere is a DNA ...

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 ...

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

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 ...

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 ...

Lampbrush Chromosomes

In 1882, Flemming observed lampbrush chromosomes (LBC) in salamander eggs. Later in 1892, R&#252;ckert observed LBCs in shark egg cells and coined the ...

Polytene Chromosomes

Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in ...

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

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the ...

Genetics of Organisms

Mendelian Genetics
Evolution is caused by changes in the genetic composition of populations. In the field of population genetics, scientists model this ...

REF and WEF Fly Genetics
ExpandTo prepare for the experiment, be sure to obtain cultures of Drosophila melanogaster at least two weeks ahead of the ...

REF and WEF Fly Genetics
ExpandNOTE: At your station, you should have four vials of flies. They will be labeled as male or female. They will also be ...

Genetic Lingo

Overview

An organism is diploid if it inherits two variants, or alleles, of each gene, one from each parent. These two alleles constitute the genotype ...

Punnett Squares

Overview

A Punnett square displays the possible genotypes offspring can inherit from two parental genotypes. If a trait&#x2019;s inheritance pattern ...

Monohybrid Crosses

Overview

In the 1850s and 1860s, Gregor Mendel investigated inheritance by performing monohybrid crosses in pea plants. He crossed two plants that were ...

Dihybrid Crosses

Overview

To determine whether traits are inherited together or separately, Gregor Mendel crossed pea plants that differed in two traits. These parental ...

Trihybrid Crosses

Trihybrid Crosses
Some of Mendel&#8217;s crosses examined three pairs of contrasting characteristics. Such a cross is called a trihybrid cross. A ...

Law of Segregation

When crossing pea plants, Mendel noticed that one of the parental traits would sometimes disappear in the first generation of offspring, called the F1 ...

Law of Independent Assortment

While Mendel&#x2019;s Law of Segregation states that the two alleles for one gene are separated into different gametes, a different question of how ...

Test Cross

Alleles are different forms of the same gene. Humans and other diploid organisms inherit two alleles of every gene, one from each parent.

An allele is ...

Chi-square Analysis

The chi-square test is a statistical hypothesis test. It is used to check whether there is a significant difference between an expected value and an ...

Pedigree Analysis

Overview

A pedigree is a diagram displaying a family&#x2019;s history of a trait. Analyzing pedigrees can reveal (1) whether a trait is dominant or ...

Nature and Nurture

Many human characteristics, like height, are shaped by both nature&mdash;in other words, by our genes&mdash;and by nurture, or our environment. For ...

Probability Laws

Overview

The probability of inheriting a trait can be calculated using the sum and product rules. The sum rule is used to calculate the probability of ...

background-and-environment-affect-phenotype

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 ...

Multiple Allele Traits

The Concept of Multiple Allelism

Multiple allelism describes genes that exist in three or more allelic forms. Although diploid organisms, like humans, ...

X and Y Chromosomes

Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 ...

Chromosomal Theory of Inheritance

In 1866, Gregor Mendel published the results of his pea plant breeding experiments, providing evidence for predictable patterns in the inheritance of ...

The Y Chromosome Determines Maleness

The Y chromosome is a sex chromosome&#160;found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human ...

Non-nuclear Inheritance

Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm⁠&mdash;such as chloroplasts and mitochondria⁠&mdash;also ...

The Ratio of X Chromosome to Autosomes

In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined ...

Incomplete Dominance

Gregor Mendel&#39;s work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid ...

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be ...

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cu&#233;not discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is ...

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological ...

Epistasis

In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence ...

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, ...

Polygenic Traits

When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered ...

Dosage Compensation

In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one ...

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause ...

Ask questions to clarify relationships about the role of DNA and chromosomes in coding the instructions for characteristic traits passed from parents to offspring. [Assessment Boundary: Assessment does not include the phases of meiosis or the biochemical mechanism of specific steps in the process.]

genome-size-and-the-evolution-of-new-genes

Genome Size and the Evolution of New Genes

Gene Families

Gene Evolution - Fast or Slow?

types-of-genetic-transfer-between-organisms

Types of Genetic Transfer Between Organisms

What is Meiosis?

Meiosis I

Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of ...

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for ...

Meiosis vs. Mitosis

Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, ...

Crossing over

Nondisjunction

Replication in Eukaryotes

Overview

In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high ...

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. [Clarification Statement: Emphasis is on using data to support arguments for the way variation occurs.] [Assessment Boundary: Assessment does not include the phases of meiosis or the biochemical mechanism of specific steps in the process.]

HS-LS3-2

Chromatin Spreading and Gene Silencing

Description

Transcript

Tags

More videos by Standards