Epigenetics and how we can turn on and off genes

The DNA in the nucleus is precisely wound, folded, and compacted into chromosomes so that it will fit into the nucleus. It is also organized so that specific segments can be accessed as needed by a specific cell type.

Epigenetics describes the physiological reprogramming that occurs in the cell without changes in the DNA sequence. The main epigenetic tools used by the cell are:

• DNA methylation
• Histone modifications
• Histone variants
• Chromatin remodeling
• Regulatory activity of microRNAs (miRNAs).

The combinative use of these tools regulates the accessibility of the DNA to outside factors in the nucleus, which affects vital cellular processes including transcription and DNA repair.

The epigenetic modifications are known as tags and they provide the instructions to the DNA.   Several of these tags have been discovered, but the two main ones involve methyl groups (made of carbon and hydrogen) and histones (a type of protein). To imagine how tags work, think of a gene as a lamp. Methyl groups act as an on-off switch that turn a gene on or off. Histones, on the other hand, act like a dimmer switch, regulating gene activity up or down. It’s thought that we have four million of these switches that are triggered by lifestyle and environmental factors.

DNA modifications that do not change the DNA sequence can affect gene activity. Environmental influences, such as a person’s diet and exposure to pollutants, can also impact the epigenome.  Epigenetic changes can help determine whether genes are turned on or off and can influence the production of proteins in certain cells, ensuring that only necessary proteins are produced. For example, proteins that promote bone growth are not produced in muscle cells. Patterns of epigenome modification vary among individuals, different tissues within an individual, and even different cells.

Our DNA is packaged by wrapping around histone proteins. Histone proteins act like a spool that DNA can be wound around to become more compact. Initially, 146 base-pairs of DNA are wrapped.Under the electron microscope, this winding of DNA around histone proteins looks like small beads on a string . These beads (histone proteins) can move along the string (DNA) and change the structure of the molecule.  Histones package and order DNA into structural units called nucleosome complexes, which can control the access of proteins to the DNA regions.  If DNA encoding a specific gene is to be transcribed into RNA, the nucleosomes surrounding that region of DNA can slide down the DNA to open that specific chromosomal region and allow for the transcriptional machinery (RNA polymerase) to initiate transcription . Nucleosomes can move to open the chromosome structure to expose a segment of DNA, but do so in a very controlled manner.  Chemical modifications to either the histone proteins or the DNA itself signals whether or not a particular region of the genome should be “open” or “closed” to the transcription machinery.

Modifications such as acetylation or methylation of the histones can alter how tightly DNA is wrapped around them, while methylation of DNA changes how the DNA interacts with proteins, including the histone proteins that control access to the region.  This type of genetic regulation is called epigenetic regulation as it does not change the nucleotide sequence of the DNA.

There are many factors that influence whether genes are turned on or off. One of these is an epigenetic process called methylation, in which a group of carbon and hydrogen atoms (a methyl group) attaches to DNA, adjusting how genes are expressed.  When methyl groups are added to a particular gene, that gene is turned off or silenced, and no protein is produced from that gene.