WELCOME TO ELEMENTAL EPIGENOMICS
TINY SPACE, IMMENSE CONTEXT
Within a nucleus just a few millionths of a meter in diameter, the amazing packaging of our ~ 2 meter long GENOME is taking place. Exquisitely executed in virtually everyone of our 300 or so trillion cells, this complex process involves DNA FOLDING and LOOPING on several levels. Besides solving the packaging issue, these systems control the presentation of genomic sequences for TRANSCRIPTION FACTOR reading.
DNA is NEVER alone...
In eukaryotic cells, DNA is intimately wrapped around HISTONES, chemically written upon, and decorated with a mind boggling array of protein and RNA complexes that control GENOME EXPRESSION. Some of these DNA interactions or modifications are very stable, while many are amazingly dynamic and change with circadian rhythm. By first understanding the basics of these modifications or the EPIGENOME, we can engineer the presentation of the genome.
Virtually all DNA can be EXPRESSED
Genome presentation allows DNA to be read, interpreted, and TRANSCRIBED or EXPRESSED. Classically described in a GENE transcription context, we now understand that genes represent only ~1% of the GENOME. Yet, scientists have recently discovered that nearly the entire genome is in fact transcribed. This means that cells are filled with far more kinds of RNA transcripts than gene messenger RNA. New RNAs=new functions, and some are epigenetic.
The BASICS
So what is the EPIGENOME?
Whereas a GENOME is the actual sequence of all DNA for an organism, an EPIGENOME governs the TRANSCRIPTION or EXPRESSION of a particular genome. It is defined as the entire collection of EPIGENETIC MODIFICATIONS and heritable factors that regulate RNA expression.
EPI-MODS
EPIGENETIC MODIFICATIONS or EPI-MODS unlock the genome. There are many and potential combinations are infinite. However, through extensive study researchers have developed a keen understanding of 4 primary types of EPIGENETIC MECHANISMS.
EPI-MODS. THE 4 "BIGS"
1. DNA Methylation
DNA METHYLATION is the quintessential epi-mod. During DNA methylation, methyl groups are enzymatically "written" onto DNA to be read by TRANSCRIPTION FACTORS. Whereas, some DNA methylation sites suppress gene transcription, others enhance expression.
2. Histone Modification
DNA is closely wrapped around HISTONES, typically 8 histones/1.6 turns of the helix to be exact. This octomer/DNA structure is termed the NUCLEOSOME, of which nucleosome position itself represents a key factor in genome access. The TAILS of HISTONES are decorated with combinations of several unique amino acid modifications. These determine DNA binding affinity and TRANSCRIPTION FACTOR recruitment.
3. Chromatin Remodeling & DNA Looping
Sometimes it's not enough to modify a HISTONE TAIL; entire NUCLEOSOMES must be moved around and ejected by unique protein complexes. DNA is further looped upon itself into active or repressive expression territories of DNA in 3D space.
4. RNA and the EPIGENOME
Now that we understand that virtually the entire genome is TRANSCRIBED. This is far more than the~ 1% that actually codes for genes. So what's up with all the extra RNA? Some of it is EPIGENETIC RNA. Some of it we‘re still discovering.