Chromatin is formed by DNA wrapped on histones (nucleosomes) and non-histone proteins.
Chromatin changes many times during the cell cycle.
Eucariotic chromosomes contain a lot of DNA in their size, each chromosome being made up of a single double helix of DNA that contains about 2 * 108 pairs of bases in the man, if the DNA molecule is stretched it would be about 6 cm long.
Histones are responsible for the first level of DNA packing, the amount of histones in the chromatin is about equal to the amount of DNA.
Histones possess amino acids with a positive charge which is why they bind to DNA that has a negative charge.
The complex DNA-logs represent the basic structure of chromatin, and in the eukaryotes there are 5 types of histones very similar to each other.
Unplugged chromatin resembles a pearl necklace, where each pearl constitutes the nucleosome, the basic packaging unit of DNA.
The nucleosome consists of DNA wrapped around a protein core in which there are 2 molecules of each of the 4 different histones (H2A, H2B, H3 and H4), while the fifth H1 histone molecule binds to the pearl close to the chromatin Assumes the next level of packing.
Histones temporarily abandon the DNA during replication and remain united to it during transcription.
Nucleosomes by modifying their shape and position allow polymerases that synthesize RNA to move along the DNA.
Thanks to the H1 helmet, the pearl necklace can wind tightly to form a fiber of about 30 nm known as chromatin fiber 30 nm.
The 30nm chromatin fiber forms in turn the loops called loop domains acting as chromosomal scaffolds made up of non-histone proteins.
The trap domains are wrapped and folded further to form the characteristic chromosome.
If the chromatin that forms part of the chromosome is very condensed, so that it can be seen from the optical microscope, it is called etherochromatin, while the least compact one is called eucromatine.
The genome organization at the DNA level
Genes are only a small part of the genome in most pluricellular eukaryotic organisms, while repetitive DNA and other non-coding sequences represent most of the eukaryotic genome (97%), unlike prokaryotes, where most DNA Genome encodes proteins, and the nucleotide sequence encoding a prokaryotic gene proceeds from start to finish without interruption.
Repetitive DNA consists of nucleotide sequences present in multiple copies in the genome, usually not within the genes.
In mammals about 10-15% of the genome consists of repetitive tandem DNA (or satellite DNA), short sequences repeated in series (eg GTTACGTTACGTTAC ...), repetitions usually not longer than 10 pairs of bases, with densities Often different from that of the rest of the DNA.
Satellite DNA is classified into 3 types depending on the total length in each site: regular satellite DNA (100000-10milion bases), minisatellite DNA (100-100000 bases), DNA microsatellite (10-100 bases).
Much of the satellite DNA is located in centromers and telomers, suggesting that it must be implicated in structural roles and because of its position it serves to protect the chromosome from degradation or disruption that would cause the loss of coding genes, in addition tandem repetitive DNA Can stretch over several generations.
The repetitive repetitive DNA is that DNA in which repeated units are not close to each other, but dispersed in the genome.
The repetitive repetitive DNA represents about 25-40% of the genome in most mammals (and they are almost all transposon sequences) and in humans there are similar sequences of this DNA called Alu elements, the only repetitive DNA encoding.
A set of identical or very similar genes is called a multigenerational family, and these families can be considered as repetitive DNA consisting of repeated units / genes.
Multigenic families made up of identical genes usually produce RNA.
Probably the family of genes originated from a single gene due to errors during duplication of DNA.
Pseudogenes have sequences very similar to normal genes but do not generate functional products.
Except for rare mutations, the nucleotide sequence of an organism's DNA remains constant throughout its life, and when mutations in somatic cells occur, they are not transmitted to the offspring since they are not genes of gametes.
In some cases, the number of genes may temporarily increase, and the selective replication of certain genes, called genetic amplification, is a powerful means of increasing gene expression, and this can be done depending on the need to produce, for example, more Ribosome to use at the moment and then degrade.
The genomic recurrence has the remainder of long stretches of DNA that cause amplification or loss of genes.
All organisms possess transposons (10% in the human genome), DNA traits that are able to move within the genome, and when a transposon jumps into a coding gene, it can block it.
Retrotrasposons are transposable elements that move into the genome by means of intermediate RNA, a transcript of DNA retrotrasposone, where, for insertion into another site, this RNA must be reconverted by reverse transcriptase.
Alu elements are retrotrasposons that do not encode reverse transcriptase but may move using encoding enzymes from other retrograde genomes.
The permanent reorganization of DNA portions occurs in the immune system developing during cell differentiation, and this is important for the efficacy of antibodies or immunoglobulins.
Control of gene expression
Each cell of a multi-celled eukaryotic organism expresses only a small part of its genes, moreover, cells of an organism must continually turn on or turn off certain genes in response to signals coming from the internal or external environment.
Gene expression is also controlled over the long term by cell differentiation, the process where cells, through shape and function changes, specialize during the development of an organism.
Chromatin serves both to pack the DNA in a compact form so that it is in the cell nucleus, either to regulate the physical state of the DNA of a gene or adjacent region, important for determining the availability of the transcription gene , Which is also influenced by the location of the gene itself.
DNA methylation involves the addition of methyl groups (-CH3) to the DNA bases after it has been synthesized, and this would seem to be a feature of inactivity of the genes, so that if they are demethylated, they reactivate.
Histamine acetylation involves the addition of acetyl groups (-COCH3) to certain amino acid of histone proteins, and when the histones are acetylated, they change to form less closely to DNA so that the transcription proteins have a Facilitated access to acetylated genes.
The transcription
The beginning of transcription is the most important and most commonly used control point of gene expression.
Control elements are non-coding DNA segments that help regulate the transcription of a gene by binding certain proteins, transcription factors.
Transcription factors are essential for the transcription of all protein-encoding genes, and only one of these factors recognizes a DNA sequence, the TATA box within the promoter, the others recognizing proteins.
Only when the assembly of the starting complex is completed, polymerase can begin coding.
Control elements increase the efficiency of promoters through the binding of additional transcription factors.
The control elements far from the promoter are called intensifiers, which can be thousands of nucleotides away.
The activator is a transcription factor that binds to an intensifying element stimulating the transcription of a gene (similarly silencers exist).
Direct transcription control depends largely on regulatory proteins that bind selectively to DNA and other proteins, and hence a transcription factor usually has a domain of DNA binding and one for proteins.
The control elements contain sequences consisting of 4 to 10 nucleotide pairs.
The operon genes are sequentially transcribed in a single mRNA molecule and are then translated together.
The co-ordinated expression of eukaryotic genes depends on the association of a specific control element or set, with each single gene of the dispersed group.
In principle, genes that have the same control elements are triggered by the same chemical signals.
Post-transcriptional mechanisms
A cell can quickly regulate gene expression in response to environmental changes, without the alteration of the transcription.
Alternative splicing of the RNA occurs when different molecules of mRNAs are produced from the same primary transcript, depending on which RNA segments are considered exons or introns.
The phases of gene expression that can be adjusted are:
- Adjustment of mRNA degradation: mRNAs in eukaryotes live from a few hours to a few weeks, its degradation begins with the enzymatic shortening of the poly (A) tail and this favors the removal of the cap at 5 ', digesting l MRNA from nucleases.
- Translation Control: Most control mechanisms block the initiation phase of polypeptide synthesis when ribosomal subunits and start tRNA bind to an mRNA.
The translation of specific mRNAs can be blocked by regulatory proteins that prevent the ribosome attack. - Maturation and degradation of proteins: Eucaryotic polypeptides often need to be modified to produce functional protein molecules, and regulation may take place at any of the stages of protein modification or transport.
Proteasomes are large protein complexes that recognize some of the proteins previously labeled and degrade because they are no longer needed for the cell.
Molecular cancer biology
Many of the mutations that cause cancer are caused by environmental influences (eg x-rays) that cause problems in regulating cell growth and division.
The genes that cause cancer are oncogenes.
Normal cellular genes, called proto-oncogens, encode proteins by stimulating normal growth and cell division.
The oncogene derives from a genetic modification leading to an increase in the amount of proto-oncogene or the growth of the activity of each protein molecule, the genetic changes that transform the proto to oncogenes are of 3 types: Inside the genome (a proto-oncogene may be close to a site that is particularly active due to chromosome breakdown, and thus increases gene transcription), amplification of a proto-oncogene (determines the increase in the number of copies of the gene in the Cell), point mutation of a proto-oncogene (modifies the protein product of the gene by producing a newer active or degradable protein).
Cancer suppressor genes are those carcinogenic genes that inhibit cell division, some repair damaged DNA, others control cell adhesion to an extracellular matrix or between them, others inhibit the cell cycle.
The product of the ras gene is a G protein that stimulates the cell cycle, and when it is produced by the ras proto-oncogene, it also activates in the absence of the growth factor.
The p53 gene works by transcription for several genes, such as p21 stopping the cell cycle, pending the activation of genes for DNA repair.
Apoptosis occurs when p53 activates suicidal genes that cause cell death when DNA damage is irreparable.
If the p53 gene is defective or absent, cancer can occur, that is, when the DNA is duplicated even if it is defective.
To produce all the characteristic changes of a tumor cell, many somatic mutations are usually needed, so the risk of cancer increases with age, because longer we live and it is more likely that it will develop due to ' Accumulation of all possible mutations.
Because a cell becomes tumorous, at least about half a dozen DNA variations must occur.
As mutant suppressor alleles are usually recessive, mutations must lead to the loss of both alleles in the cell genome to stop tumor suppression.
Most oncogenes behave as dominant alleles.
In many malignant tumors telomerase is activated, the enzyme that exposes the erosion of the extremities of the chromosome, making the tumor cell immortal.
Viruses seem to play an important role in at least 15% of cancer cases in the world, they contribute to the development of cancer by integrating their genetic material into the DNA of the infected cells.