Histones are alkaline proteins which play an important role in the packaging of DNA and the regulation of genes in eukaryotic organisms. Without histones, the unwound DNA in chromosomes would be very long, about 2 meters in length per cell. As a result, chromatin in the DNA is very tightly associated with these histone proteins, which package and order the DNA into structural units called nucleosomes. This supercoiled, condensed structure allows for the long DNA molecule to fit inside the nucleus. Selective winding and unwinding allows for portions of the DNA to be exposed. In this way, histones also play a role in regulating gene expression.
All Eukaryotes have five major classes of histones, each differing in molecular weight and amino acid composition. These classes are H1, H2A, H2B, H3, and H4. By using X-ray crystal structure, we are able to see that the bead on each nucleosome contains eight histone molecules, and two copies each of H2A, H2B, H3, and H4. This provides a repeating unit of about 200 base pair, of which 146 base pair are bound tightly around the eight-part histone core [1] and the remainder serves as linker DNA between nucleosome beads. The crystal structure deduced is shown below:
The eight histone proteins are shown in different colors, where blue represents H3, green represents H4, yellow represents H2A, and red represents H2B. The DNA double helix can be seen wound around the nucleosome core.
Besides the core histones, there also exists the linker histone, H1. This allows for multiple nucleosomes to be linked to each other. As a result, DNA is locked into place. Interestingly, histone H1 is very important in stabilizing chromatin higher-order structures, and 30-nanometer fibers form mo...
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Histone modification may or may not be dependent on DNA methylation and is difficult to detect compared to LOH.
The epigenome marks the genome, determining whether or not a gene is expressed and if so, to what level. It does this in two ways, DNA methylation, and histone modification. DNA methylation is where a methyl group, a tag of carbon and hydrogen, connects to a part of DNA (to the gene) and decides for it to be expressed or not. Histone modification is where a chemical tag secures a histone, or a protein, and tightens or loosens the gene's coil around it to determine how greatly the gene is expressed.
Histone acetylation and deacetylation are two ways to modify histones on chromosomes, thereby regulating genetic expressions. Butyrate was reported as a non-competitive, reversible histone deacetylases (HDAC) inhibitor [19-21], additionally other HDAC inhibitors, such as sodium valproate, sulforaphane, apcidin etc., were examined as the genetic expression promoters [22-25]. In our study, we determined the effects on HBD1 and LL-37 expression induced by seven HDAC inhibitors (Figure 4).
Acetylation is mediated by histone acetyltransferases (HATs) which act as coactivators for transcription by interacting with the DNA-binding activators. Acetylation catalyzes the transfer of an acetyl group to the ε-amino group of the lysine residue with the utilization of the acetyl CoA as cofactor.Example: H3K56 acetylation by p300/CBP. HDACs have opposite effects to that of HATs, and remove the acetyl group from the lysine residues.
Groups of transcription factor binding sites called enhancers and silencers can turn a gene on/off in specific parts of the body.
Zhao X, Su J, Wang F, Liu D, Ding J, et al. (2013) Crosstalk between NSL Histone Acetyltransferase and MLL/SET Complexes: NSL Complex Functions in Promoting Histone H3K4 Di-Methylation Activity by MLL/SET Complexes. PLoS Genet 9(11): e1003940. doi:10.1371/journal.pgen.1003940
...Glass, Non-coding RNAs as regulators of gene expression and epigenetics, 2011, oxford journals, 90 (3), p430-440
... T., Sheikhattar, R., & Shilatifard, A. (2009). An operational definition of epigenetics. Genes and Development, 781-783. Retrieved from http://genesdev.cshlp.org/content/23/7/781.long
Also, my Genetics lab this semester is doing research on yeast with my teacher Dr. Duina. The goal of our research is to uncover the mechanisms that regulate the interaction between different proteins. The proteins that we will be looking at are histone chaperones, transcription elongation factor Spt16, and the chromatin that is contained in the RNA Polymerase II. We will be using the Saccharomyces cerevisiae yeast. At the end of the semester, I will be writing a research paper on the results of our
Epigenetic inheritance is defined as the regulatory information passed down from parent to offspring without any changes in the underlying DNA sequence. This process can involve various modifications of histones as well as DNA itself. These types of alterations include acetylation, methylation and phosphorylation. Such changes can regulate expression through a variety of different mechanisms, including controlling how accessible the DNA is to transcription factors (1). Epigenetic regulation is a highly prevalent method of controlling gene expression, and a vast number of diseases involve disturbances in the epigenome (2).
A chromosome is made up of two identical structures called chromatids. The process of nuclear division is called interphase; each DNA molecule in a nucleus makes an identical copy of itself. Each copy is contained in the chromatid and a characteristic narrow region called the centromere holds the two chromatids together. The centromere can be found anywhere along a chromosome but the position is the characteristic for a particular chromosome. Each Chromatid contains one DNA molecule. DNA is the molecule of inheritance and is made up of a series of genes. The fact that the two DNA molecules in the sister chromatids, and hence their genes, are identical is the key to precise nuclear division.
Areas of non-structural DNA, previously known as junk DNA, are now known to be active and able to control gene expression and this is also true of small RNA molecules which act upon messenger RNA by RNA editing (Pinel, 2014). Other mechanisms that regulate gene expression include the widely studied methods of DNA methylation (decreases adjacent gene expression) and histone remodeling (increases or decreases expression) (Pinel, 2014). The final product of genetic expression or regulation can be seen in the example of a caterpillar culminating into a butterfly (Nisic, 2009). They both have the exact DNA, however, the regulation of expression of certain genes during maturation produces the final state of butterfly. As epigenetics continues to examine the process of genetic inheritance and expression, I believe it will transform how we
The cell is the fundamental structural unit of all living organisms. Some cells are complete organisms, such as the unicellular bacteria and protozoa; others, such as nerve, liver, and muscle cells, are specialized components of multi-cellular organisms. Cells range in size from the smallest bacteria-like mycoplasmas, which are 0.1 micrometer in diameter, to the egg yolks of ostriches, which are about 8 cm (about 3 in) in diameter. Although they may differ widely in appearance and function, all cells have a surrounding membrane and an internal, water-rich substance called the cytoplasm, the composition of which differs significantly from the external environment of the cell. Within the cell is genetic material, deoxyribonucleic acid (DNA), containing coded instructions for the behavior and reproduction of the cell and also the chemical machinery for the translation of these instructions into the manufacture of proteins. Viruses are not considered cells because they lack this translation machinery; they must parasitize cells in order to translate their own genetic code and reproduce themselves.
Citation: Philips, T. (2008) Regulation of Transcription and gene expression in Eukaryotes. Nature Education 1(1)
A recent field of biology, called epigenetics, is rapidly transforming previous ideas on the impact of genes. The...