Structural Biochemistry/Epigenome reader
As mentioned in the main page, the epigenome is made up of chemicals that tell your genome what to do. Your genome is basically the same in all of your cells, so what makes your cells different in the way they behave is epigenome which controls them. An example of epigenomics would be to look at a set of monozygotic twins. Their genome are identical, yet due to exposure to different environmental factors as they grow up, they will experience different epigenetic changes, which may make one of the twins more susceptible to developing certain diseases that the other would be less likely to get. This is why many find it important to study the epigenome and there are many programs funded to catalogue the human epigenome, in hopes that we can understand and learn what genes are being turned on and off and how that affects us. Right now there are multiple ways that are being used to read the epigenome. The PHD finger is one of the ways.
PHD zinc fingers
In the article “The PHD finger: a versatile epigenome reader” written by Roberto Sanchez and Ming-Ming Zhou, they discuss how the plant homeodomain (PHD) zinc fingers that they studied were found to able to read complex histone sequences. Activation and silencing of gene transcription is controlled by modifications of histones, H2a, H2B, H3, and H4. Histones are proteins that pack and organize DNA into nucleosomes. Histones can be modified by adding a methyl group to the amino acid lysine, or adding an acetyl group to the amino acids lysine or arginine. PHD fingers have evolved to recognize when, in the histone, those amino acids have been methylated or acetylated. Main cites that are methylated on the histone H3 tail are K4 and R2.
Out of the four modifications to histones mentioned before, PHD fingers (a small protein domain whose structure is stabilized by zinc atoms) can read histone H3. PHD does this by binding to the first six N terminal residues of the histone. Ligands are molecules that bind to a central metal. This is important because bromodomain PHD finger transcription factor (BPTF) is a PHD finger bound to its ligand, and it has the ability to bind to H3 when K4 is methylated and R2 is not. Most of these PHD fingers have an aromatic cage that helps with binding. Those that don’t however, have the ability to bind to K4 when it is not methylated. There are many different types of PHD fingers that will bind depending on what amino acids are methylated and/or acetylated. When they bind, the conformation changes slightly, allowing one to distinguish between them.
Further study is still required to completely understand how PHD fingers work.
- National Human Genome Research Institute http://www.genome.gov/27532724
- Bonetta, Laura (2008). "Epigenomics: The new tool in studying complex diseases". Nature Education 1 (1): 178. http://www.nature.com/scitable/topicpage/epigenomics-the-new-tool-in-studying-complex-694.
- Human Epigenome Project http://www.epigenome.org/
- Sanchez, Roberto; Zhou, Ming-Ming (2011). "The PHD finger: A versatile epigenome reader". Trends in Biochemical Sciences 36 (7): 364–72. doi:10.1016/j.tibs.2011.03.005. PMID 21514168.