EPIGENETIC MECHANISMS – DNA METHYLATION & HISTONE MODIFICATION
Individual cells encode their epigenetic information through modifications to either the DNA itself or histones, the proteins that DNA coil around. One other epigenetic mechanism that has recently been discovered is regulating micro RNA, which won’t be discussed here.
Currently, DNA methylation is one of the most well-understood epigenetic modifications that dates back to studies conducted by Griffith and Mahler in 1969, which suggested that this methylation of DNA may be important for long-term memory. DNA methylation is a common regulatory mark found in many different cell types on the 5-carbon of cytosine residues (5-mC) at cytosine–phosphate–guanine dinucleotides (CpGs) in DNA. DNA methylation is essential in genomic imprinting, gene expression regulation, X chromosomal inactivation, and embryonic development. This epigenetic mark can activate or repress gene transcription at specific sites based on the methylation levels at promoter regions.
Hypermethylation at promoters blocks access of transcriptional machinery and thus inhibits gene expression. Conversely, hypomethylation facilitates gene activation as a result of increased accessibility of DNA by polymerase. The regulation of DNA methylation is essential to normal cell function in somatic cells, gametes, and the embryo. The DNA methyltransferase (DNMT) family of proteins helps to facilitate de novo methylation and methylation maintenance. The enzymes directly responsible for de novo methylation include DNMT3A, DNMT3B, and DNMT3L. Both DNMT3A and DNMT3B contain catalytic domains, which allow them to directly lay down new methylation marks. DNMT3L is essential in directing the proper placement of marks by working in concert with DNMT3A and DNMT3B. Once methylation marks have been established, DNMT1 maintains those marks through cell division.
Histones can be modified through a number of post-translational mechanisms including lysine and arginine methylation, serene and threonine phosphorylation, lysine acetylation, and lysine ubiquitination and sumoylation. These modifications occur primarily within the histone amino-terminal tails protruding from the surface of the nucleosome as well as on the globular core region. These different modifications to the histones are thought to impact chromosome function through a couple of different mechanisms. The first mechanism alters the electrostatic charge of the histone and causes a structural change within the histone or their binding to the DNA. The second mechanism suggests modifications to binding sites for protein recognition modules that recognize acetylated or methylated lysines. Like DNA methylation, these posttranslational modifications of histones can create an epigenetic mechanism for the regulation of a variety of normal and disease-related processes.
A great brief (2:00) video on epigenetics:
The Epigenome At A Glance
Epigenetics from SciShow 9:28
The Epigenetics of Identical Twins 4:41
Learn.Genetics – Genetic Science Learning Center from University of Utah Health Sciences
The Epigenetics Revolution: How Modern Biology is Rewriting Our Understanding of Genetics, Disease and Inheritance. 2011, Nessa Carey. This is an outstanding book for anyone interested in starting to learn about epigenetics. I can’t recommend this too highly. It is wonderful.
Epigenetics: How Genes and Environment Interact. NIH Videocast, April 18, 2012. 58:00.