Chromatin: what is its structure, type and function? (2023)

Chromatin is the combination of DNA and proteins that make up the contents of the cell nucleus. The main functions of chromatin are to package DNA into a smaller volume suitable for cells, to strengthen DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene expression and DNA replication.

The main protein components of chromatin are histones, which condense DNA. Chromatin is only found in eukaryotic cells.

Prokaryotic cells have a very different DNA structure known asgene pool(chromosomes without chromatin).

The structure of chromatin depends on several factors.

The overall structure depends on the phase of the cell cycle, and during interphase the chromatin structure loosens, allowing RNA and DNA polymerases to transcribe and transcribe.copy DNA。

chromatin structure

The local structure of interphase chromatin depends on the genes present in the DNA: actively transcribed ("en") DNA-coding genes are, and have been found to be, more loosely packed.RNA polymerase(known aseuchromatin), while DNA encoding inactive (“off”) genes is associated with structural proteins and is more densely packed (heterocromatina）。

Epigenetic chemical modifications of chromatin structural proteins also alter local chromatin structure, particularly histone chemical modifications through methylation and acetylation. As cells prepare to divide, that is, enter mitosis or meiosis, the chromatin packs more densely to facilitate the separation of chromosomes at later stages.

As a result, at this stage of the cell cycle, the individual chromosomes of many cells become visible under the light microscope.

In general, the organization of chromatin is divided into three levels:

1. DNA encapsulates histones and forms nucleosomes; a "pearls on a string" structure (euchromatin).

2. Various histones are packed into 30 nm fibers composed of nucleosome assemblies (heterochromatin) in their most compact form.

3. The 30 nm fibers undergo a greater degree of DNA packaging in metaphase chromosomes (during mitosis and meiosis).

However, there are many cells that do not follow this organization. For example, bird sperm and red blood cells have more compact chromatin than most eukaryotic cells.trypanosomes-protozoaIt does not condense its chromatin into chromosomes visible for mitosis.

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The optimized structure of chromatin during interphase allows DNA repair and transcription factors to easily access the DNA while condensing it in the nucleus. The structure varies depending on how the DNA needs to be obtained. Genes that require regular access by RNA polymerase require the more flexible structure offered by euchromatin.

structural change

The structure of chromatin undergoes several changes. Histones are the building blocks of chromatin that alter DNA packaging through various post-translational modifications. Acetylation relaxes chromatin, facilitating replication and transcription.

When certain residues become methylated, they hold DNA tightly together and restrict access to various enzymes. A recent study revealed the presence of a bivalent structure in chromatin: methylated lysine residues at positions 4 and 27 of histone 3.

It is believed that this could be relevant to development; Lysine 27 methylation is higher in embryonic cells than in differentiated cells, whereas lysine 4 methylation positively regulates transcription through the recruitment of nucleosome remodeling enzymes and histone acetylases.

Polycomb proteins play a role in gene regulation by modulating chromatin structure.

DNA structure

Most of the DNA in cells is the normal DNA structure. However, in nature DNA can form three structures: DNA-A, DNA-B and DNA-Z. The A and B chromosomes are very similar and form a right helix, while Z DNA is a more unusual left helix with a zigzag phosphate backbone. Due to the nature of the connection between B-DNA and Z-DNA, Z-DNA is believed to play a specific role in chromatin structure and transcription.

At the junction of B-DNA and Z-DNA, a base pair slips out of normal bonding. They serve dual roles as recognition sites for many proteins and as torsion stress sinks via RNA polymerase or nucleosome binding.

Nucleosomes and "Pearls"

The basic repeating elements of chromatin are nucleosomes, linked together by the splicing of DNA segments, a much shorter arrangement than pure DNA in solution. In addition to the core histones, there is the linker histone H1, which contacts the exit/entry of the DNA strands in the nucleosome. Together with histone H1, the nucleosomal core particle is called a chromosome. Nucleosomes have about 20 to 60 base pairs of DNA attached to them and can form "bead-like" fibers about 10 nm in length under non-physiological conditions.

Nucleosomes bind to DNA non-specifically as required by their role in the overall packaging of DNA. However, large DNA sequence preferences exist to control the positioning of nucleosomes. This is mainly due to the different physical properties of different DNA sequences: adenosine and thymine, for example, pack more easily into the internal minor groove. This means that nucleosomes can bind preferentially at one position every 10 base pairs (the helical repeats of DNA), where the DNA rotates to maximize the number of A and T bases in the internal minor groove.

30 nm phases

With the addition of H1, the "bead" structure coils back into a 30 nm diameter helical structure, called a 30 nm fiber or filament. The exact structure of chromatin fibers in cells is unknown and remains controversial.

This level of chromatin structure is believed to be the form of euchromatin that contains actively transcribed genes. EM studies have shown that 30 nm fibers are highly dynamic, unfolding into 10 nm fiber structures (“beads on a string”) when traversed by RNA polymerase involved in transcription.

Existing models generally assume that nucleosomes are perpendicular to the fiber axis and that linker histones line the interior. The 30 nm stable fibers are based on the regular positioning of the nucleosomes with the DNA.

Ligated DNA is relatively resistant to bending and rotation. As a result, the length of the attached DNA is critical to fiber stability and requires that the nucleosomes be separated by a length that allows them to rotate and fold into the desired orientation without undue stress on the DNA.

• What is the normal precision of DNA replication?
• What is DNA polymerase and its role in DNA replication?

From this point of view, different lengths of adapter DNA should result in different folding topologies of chromatin fibers. Recent theoretical work based on electron microscopy imaging of reconstituted fibers supports this idea.

Spatial organization of chromatin in the cell nucleus.

The arrangement of the genome in the nucleus is not random: certain regions of the genome tend to be in certain spaces. Certain regions of chromatin are enriched in the nuclear envelope, while other regions are held together by protein complexes.

However, this arrangement has only been well characterized in female mammals, where one of the two X chromosomes is condensed within Barr.

As a result, these genes are permanently turned off and women do not receive a "double dose" compared to men. There is some debate as to how much idle X is actually compressed.

transcription explosion

Fluctuations between open and closed chromatin can lead to interruptions or bursts of transcription. Other factors may also play a role, such as the association and dissociation of transcription factor complexes with chromatin.

Unlike simple probabilistic transcription models, this phenomenon could explain the high variability in gene expression between cells in isogenic populations.

metaphase-chromatin

The metaphase structure of chromatin differs significantly from that of interphase. Optimized for physical strength and driveability, it forms the classic chromosome structure seen on karyotypes.

The structure of the condensed chromosome is believed to be a 30 nm fibrous ring attached to a core protein structure. However, its properties are not well defined.

The physical strength of the chromatin is critical at this stage of division to prevent DNA damage when the daughter chromosomes separate. To maximize potency, chromatin composition changes as it approaches the centromere, primarily through substitution of histone H1 analogues.

It should also be noted that while most of the chromatin is highly condensed during mitosis, there are small areas that are not as densely condensed. These regions normally correspond to the promoter regions of genes that are active in that cell type prior to entry into mitosis.

Lack of compression in these regions is called marking, an epigenetic mechanism thought to be important for passing on the "memory" of which genes were active before entering mitosis to daughter cells. Since transcription stops during mitosis, this marking mechanism is necessary to support the transmission of this memory.