Name: cenp-a and centromere identity
Uploaded: 2020-11-23T11:47:35.000Z
Duration: 2 min 30 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 Variants at the Centromere

The centromere is a constricted region on each chromosome where the kinetochore and microtubules assemble to ensure faithful separation of the chromatids during anaphase of cell division.&#160;
In most eukaryotes, the centromere is partitioned into two chromatin domains- the centromere core and the pericentric heterochromatin region.
The centromere core in all eukaryotes contains a variant of core histone H3, called Centromere Protein A or CENP-A. Together with the three other core histones H2A, H2B, and H4, the CENP-A forms the centromere-specific nucleosome.&#160;
The functional C-terminal fold domain of the CENP-A is highly conserved among eukaryotes. However, the N-terminal tail of the protein shows significant variations both in size and sequence.
The centromere cores in the yeast Saccharomyces cerevisiae contain a single CENP-A nucleosome attached to a single mitotic spindle; hence, these are referred to as point centromeres.&#160;
This core centromere region is flanked by approximately 125 bps of AT-rich pericentric DNA sequences. This region is characterized by nucleosomes containing methylated histone H3.
The centromere chromatin forms a three-dimensional structure to expose CENP-A conta

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 replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also increasingly being studied.
Histone H3 variant: CENP-A
Centrosomal chromatin contains a specialized histone protein called CENP-A which shares 60% similarity with canonical histone H3. It is essential for kinetochore assembly and subsequent binding of microtubules. It is also hypothesized that CENP-A acts as an epigenetic mark to maintain centromere identity. The CENP-A is recognized and targeted to centromere via the CENP-A targeting domain (CATD).
In vitro studies have shown that centromeric nucleosomes form octomers with two copies of CENP-A along with two copies of H2A, H2B and H4 histones. Nevertheless, new studies in different eukaryotes have led to several competing models for the structure of CENP-A containing nucleosomes. According to the hemisome model, the nucleosome contains only one copy of each histone, forming a tetramer. In addition, recent studies have shown that CENP-A nucleosomes are cell cycle-regulated. They exist as octamers in S-phase and as hemisomes during other phases of the cell cycle.
Deregulation of CENP-A functions is linked to chromosome instability and cancer. Several pieces of evidence indicate overexpression of CENP-A in colon cancer, adenocarcinoma, testicular germ cell tumors, breast cancer and hepatocellular carcinoma.

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

Education

JoVE Core

Molecular Biology

Unit 1

DNA and Chromosome Structure

KEY TERMS AND CONCEPTS

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 CATD, which helps direct CENP-A to the centromere.

Studies of centromeric nucleosomes have shown more than one possible structure. In vitro studies found octamers with two CENP-A copies, along with two copies each of H2A, H2B, and H4. Other studies in different eukaryotes support competing models, including the hemisome model, in which the nucleosome has one copy of each histone and forms a tetramer.

CENP-A nucleosomes also change with the cell cycle. They appear as octamers in S-phase and as hemisomes during other phases of the cell cycle. When CENP-A function is not properly regulated, chromosome instability can result, and this has been linked to cancer. Reported examples include colon cancer, adenocarcinoma, testicular germ cell tumors, breast cancer, and hepatocellular carcinoma.

CENP-A and Centromere Identity

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 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...

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 the histone H3 variant CENP-A helps form centromeres, build kinetochores, and support chromosome stability during cell division.

CENP-A and Centromere Identity | JoVE K12

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Alabama Course of Study Science

9-12

Biology

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From Molecules to Organisms: Structures and Processes

9-12.B.1.2.b

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-LS1-1.

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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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

Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of ...

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

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 ...

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 ...

Punnett Squares

Monohybrid Crosses

Dihybrid Crosses

Trihybrid Crosses

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Law of Independent Assortment

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Polygenic Traits

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Background and Environment Affect Phenotype

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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.

X and Y Chromosomes

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The Y Chromosome Determines Maleness

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The Ratio of X Chromosome to Autosomes

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X-linked Traits

Sex Linked Disorders

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 ...

X-inactivation

What is Meiosis?

Meiosis is the process by which diploid cells divide to produce haploid daughter cells. In humans, each diploid cell contains 46 chromosomes, half from ...

Meiosis I

Meiosis II

Meiosis vs. Mitosis

Crossing Over

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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

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The Replisome

Proofreading

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Replication in Prokaryotes

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Apply concepts of statistics and probability to explain the variation and distribution of expressed traits in a population. Emphasis is on distribution and variation of traits in a population and the use of mathematics (e.g., calculations of frequencies in Punnett squares, graphical representations) to describe the distribution.

HS-LS3-3

CENP-A and Centromere Identity

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