Chromatin Structure and Role in Gene Regulation

Chromatin is a complex of RNA DNA and protein can be seen in eukaryotic cells. Its prime function is packaging very long DNA molecules into a denser, compact shape which stops the strands from becoming tangled and plays vital roles in strengthening the DNA during cell division, avoiding DNA damage, and controlling gene expression and DNA replication. In meiosis and mitosis, chromatin helps in accurate separation of the chromosomes in anaphase; the typical shapes of chromosomes visible during this stage is the result of DNA being looped into highly condensed systems of chromatin.

The prime protein constituents of chromatin are histones, which attach to DNA and act as "anchors" around which the components are wound. In common,

Three Stages of Chromatin Organization

1. DNA wraps around histone proteins, making nucleosomes and the known as "beads on a string" structure (euchromatin).

2. Several histones wrap into a 30-nanometer fiber containing nucleosome arrays in their most solid form (heterochromatin).

3. Higher-level DNA supercoiling of the 30-nm fiber creates the metaphase chromosome (throughout mitosis and meiosis).

Various organisms do not follow this organization system. For instance, avian red blood cells and spermatozoa are more tightly packed, chromatin than most trypanosomatid, eukaryotic cells and protozoa do not shrink their chromatin into visible chromosomes at all. Prokaryotic cells have completely different structures for shaping their DNA (the prokaryotic a chromosome is equal and is called a gonopore and is confined within the nucleoid region).

The simple structure of the chromatin system rests on the stages of the cell cycle. During interphase, the chromatin is structurally loose to permit access to  DNA and RNA polymerases that copy and replicate the DNA. The simple structure of chromatin in interphase depends on the exact genes present in the DNA. DNA has the genes which are not tightly compacted and closely related with RNA polymerases in a structure called euchromatin, while regions having inactive genes are usually more condensed and linked with structural proteins in heterochromatin. Epigenetic alteration of the structural proteins in chromatin through acetylation and methylation also alters confined chromatin structure and therefore gene expression. The structure of chromatin systems is presently poorly understood and is the hot topic in research in molecular biology.

Dynamic Structure 

Chromatin undergoes few structural changes throughout a cell cycle. Histone proteins are the general packer and coordinator of chromatin and can be altered by numerous post-translational changes to alter chromatin packing. Most of the modifications take place on the histone tail. The consequences in terms of chromatin availability and compaction depend both on the amino-acid that is altered and the kind of modification. For instance, Histone acetylation results in loosening and rising accessibility of chromatin for duplication and transcription. Lysine tri-methylation may either be associated with transcriptional activity (tri-methylation of Lysine 4histone H3) or transcriptional suppression and chromatin compaction (tri-methylation of Lysine 9 or 27histone H3). Numerous studies suggested that different modifications could happen at the same time. For instance, it was suggested that a bivalent structure (with tri-methylation of both histone H3 on Lysine 4 and 27) was involved in mammalian primary development.

Polycomb class proteins play a part in controlling genes via modulation of chromatin structure.

DNA Structure

In nature, DNA can form 3 arrangements, A-, B-, and Z-DNA. A- and B-DNA are very alike, creating right-handed helices, while Z-DNA is a left-handed helix with a zigzag phosphate pillar. Z-DNA is believed to play a precise role in chromatin structure and transcription because of the attributes of the junction among B- and Z-DNA. At the point of B- and Z-DNA, one pair of bases is tossed out from simple bonding. These play a double role of a point of recognition by various proteins and as a sink for torsional stress from nucleosome binding or RNA polymerase.

Nucleosomes 

The basic recurrence component of chromatin is the nucleosome, connected by sections of linker DNA, a far shorter arrangement than pure DNA in the mixture.

In core histones, there is the linker histone, H1, which links the entry/ exit of the DNA strand on the nucleosome. The nucleosome central particle, together with histone H1, is also called a chromatosome. Nucleosomes, with around 20 to 60 base pairs of linker DNA, can produce, under non-physiological conditions, an about 10 nm "beads-on-a-string" fiber.

The nucleosomes attach to DNA non-specifically, as required by their role in general DNA packaging. There are, still, large DNA sequence favorites that regulate nucleosome positioning. This is due mainly to the changing physical properties of different DNA sequences: For example, thymine and adenine are more favorably packed into the inner minor grooves. This means nucleosomes can attach preferentially at one position about every 10 base pairs (the helical repeat of DNA)- where the DNA is rotated to maximize the amount of A and T bases that will lie in the inner small groove.

Cell-Cycle Structural Organization

1. Interphase: The structure of chromatin throughout the interphase of mitosis is optimized to allow simple access of transcription and DNA repair aspects to the DNA while squeezing the DNA into the nucleus. The structure differs, depending on the access needed to the DNA. Genes that require fixed access by RNA polymerase are required to have the looser structure delivered by euchromatin.

2. Metaphase: The metaphase structure of chromatin differs massively to that of interphase. It is optimized for manageability and physical strength forming the classic chromosome structure observed in karyotypes. The structure of the compressed chromatin is believed to be loops of 30 nm fiber to central support of proteins. It is, still, not well-characterized. The physical strength of chromatin is important for this stage of the division to avoid shear damage to the DNA as the daughter chromosomes are divided. To maximize strength the arrangement of the chromatin changes as it reaches the centromere, primarily through alternative histone H1 equivalents. It should also be remembered that, in mitosis, while most of the chromatin is closely compressed, there are minor regions that are not as closely compacted. These areas often link to promoter areas of genes that were living in that cell type earlier to entry into chromatids. The shortage of space in these areas is called bookmarking, which is an epigenetic mechanism thought to be significant for transmitting to daughter cells the "memory" of which genes were active earlier to enter into mitosis. This bookmarking mechanism is required to help spread this memory because transcription terminates during mitosis.

Chromatin in Mitosis

1. Prophase

In prophase of mitosis, chromatin fibers turn into coiled chromosomes. Each duplicated chromosome contains two chromatids combined or linked at a centromere.

2. Metaphase

Throughout the metaphase, the chromatin develops extremely condensed. The chromosomes line up at the metaphase plate.

3. Anaphase

Throughout anaphase, the paired chromosomes or sister chromatids divide and are pulled by the spindle microtubules to opposite ends of the cell.

4. Telophase

During telophase, every new daughter chromosome is divided into its own nucleus. Chromatin fibers uncoil and develop less condensed. Following cytokinesis, two genetically equal daughter cells are formed. Every cell has a similar number of chromosomes. The chromosomes continue to uncoil and elongate creating chromatin.

Chromatin, Chromosome, and Chromatid

People often have trouble distinguishing the transformation between the word chromatin,  and chromatid chromosome. While all three structures are made up of DNA and can be found within the nucleus, each is exclusively defined.

• Chromatin is made of DNA and histones that are packaged into thin, fibrous fibers. These chromatin fibers are not compressed but can occur in either a compact type (heterochromatin) or less compact type      (euchromatin). Processes comprising of DNA replication, transcription, and recombination take place in euchromatin. Throughout the cell division, chromatin compresses to form chromosomes.

• Chromosomes are single-stranded groupings of compressed chromatin. Throughout the cell division progressions of mitosis and meiosis, chromosomes duplicate to make sure that each new daughter cell has the correct number of chromosomes. A replicated chromosome is double-stranded and has the familiar X form. The two strands are equal and connected in a central region called the centromere.

• A chromatid can be of the two strands of a replicated chromosome. Chromatids joined by a centromere are called sister chromatids. At the end of cell division, sister chromatids divide, becoming daughter chromosomes in the newly formed daughter cells.

Euchromatin and Heterochromatin

Chromatin inside a cell may be condensed to varying degrees depending on a cell's stage in the cell cycle. In the nucleus, chromatin occurs as euchromatin or heterochromatin. Throughout the interphase of the cycle, the cell is not separating but experiencing a period of growth. Most of the chromatin is in a less compressed form called euchromatin. More of the DNA is visible in euchromatin permitting replication and DNA transcription to occur. In transcription, the DNA double helix unwinds and opens to allow the genes coding for proteins to be replicated. DNA replication and transcription are required for the cell to make DNA, proteins, and organelles in preparation for cell division. A small percentage of chromatin present as heterochromatin in interphase. This chromatin is strongly packed, not allowing gene transcription to occur. Heterochromatin stains are darker with dyes than euchromatin.