Name: chromatin folding shapes gene activity
Uploaded: 2020-11-23T11:47:35.000Z
Duration: 2 min 35 s
Channel: JoVE

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From Molecules To Organisms: Structures And Processes

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Chromatin Position Affects Gene Expression

Gene expression is regulated at multiple levels, starting at transcription initiation and moving all the way through to the translation of mature mRNA into a functional protein.&#160;
However, not all of the enzymes required for gene expression and regulation are distributed equally in the nucleus. Instead, they are limited to spatially defined foci.&#160; This results in non-overlapping &#34;territories&#34; in the nucleus, with specific biochemical activity.&#160;
For example, the genes coding for ribosomal RNA present on chromosomes 13,14,15, 21 and 22, also known as nucleolar organizer regions, are clustered in the nucleolus - the cell&#39;s ribosome formation site.&#160;
This means that chromatin can be repositioned to such functionally distinct foci for coordinated gene expression and regulation.&#160;
However, chromatin can also extend outside its territory, forming an extended loop that can alter the gene expression pattern.
For instance, the human gene CFTR is located at the nuclear periphery in the cells where it is silent. However, in cells where the gene is expressed, the chromatin containing this region is repositioned towards the interior.
Most eukaryotic cells have multiple chromatin fibers with distinc

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 nucleus greatly influences&#160; access to genetic information. Generally, the nucleus&#39; periphery is considered transcriptionally repressive, while the cell&#39;s interior is considered a transcriptionally active area.&#160;
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of gene expression in eukaryotes. For example, the gene promoters are organized physically separate from their regulatory DNA elements, such as enhancers. These promoter-enhancer elements need to be brought together to carry out gene expressions. Each chromatid comprises several such interacting units, termed as Topologically associated domains (TADs). In some instances, TADs from two chromatids may also interact with each other.
Chromosome Territories (CT)
Several TADs accumulate to form the chromosomal territories (CT). These spatial arrangements and distributions make nucleus a heterogeneous body with distinct biochemical activities. The positioning of genes inside the CT and the positioning of CTs itself affects gene expression. In humans, the actively transcribed genes tend to localize towards the periphery of their CT. Noncoding genes tend to localize towards their CTs&#160;interior. For example, in the human female amniotic fluid cell nuclei, the ANT2 gene is found on the inactive X chromosome. When the ANT2 gene is localized towards the periphery of CT, it results in its active transcription.
Chromatins are dynamically repositioned inside the nucleus. Even the terminally differentiated cells that can no longer divide exhibit chromatin or gene repositioning. This means that the repositioning is not a random event but a coordinated molecular mechanism.

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 ...

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Molecular Biology

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DNA and Chromosome Structure

KEY TERMS AND CONCEPTS

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 promoter and enhancer regions must come together.

These interacting regions are organized into Topologically Associated Domains, or TADs. A TAD is a unit of chromatin that contains DNA elements that can interact with each other. In some cases, TADs from two chromatids can also interact.

Several TADs combine to form chromosome territories, or CTs. These territories create a nucleus with different biochemical zones. Gene location within a CT matters, and the position of the CT itself can also affect gene expression.

In humans, actively transcribed genes often sit near the edge of their CT. Noncoding genes tend to remain in the CT interior. One example is the ANT2 gene in human female amniotic fluid cell nuclei, where it is found on the inactive X chromosome. When ANT2 is positioned near the CT periphery, it becomes actively transcribed.

Chromatin can move to new positions inside the nucleus over time. This repositioning can happen even in terminally differentiated cells that no longer divide. The movement is not random. It is part of a coordinated molecular mechanism that helps control gene expression.

Chromatin Folding Shapes Gene Activity

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

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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

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chromosome replication

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the nucleosome

How DNA Is Packed into Nucleosomes

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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 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 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 chromatin folding, TADs, and chromosome territories affect gene expression in eukaryotic cells, with the ANT2 gene as an example.

Chromatin Folding Shapes Gene Activity | JoVE K12

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Chromatin Folding Shapes Gene Activity

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