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Epigenetics – Histones and Nucleotides

28 Sep 2014 by Krystal Barter
Epigenetics – Histones and Nucleotides

Joanne Holahan, Nurse and Pink Hope Ambassador, covers histones and nucleotides as part of her research into epigenetics.

Epigenetics

Histone modification also play an important role in epigenetic regulation. Histones are proteins found in the cell that package and order DNA. They are the chief protein components of chromatin which acts as the structure that DNA wraps around and plays an important role in gene regulation (3, 13, 16). These chromatin modifications play an instructive role in the repair, transcription and replication of DNA. Studies have shown that histone modification levels are predictive for gene expression and can lead to a more looser or tighter structure resulting in activation or suppression of gene expression (3). So when genes are tightly associated with histones the gene reading mechanism can’t get access. Different chemical changes on the surface of histones can change the association of proteins with particular area of DNA (3, 5, 7). Mutations in histone modification patterns have been linked to cancers and are also providing prognostic and diagnostic information in cancers (7, 13, 17, 18).Epigenetics 1

Noncoding RNAs or microRNAs (miRNA) are groups of molecules that when linked together form the building blocks of DNA or RNA (7, 13, 16). These groups are known as nucleotides and are essential for gene expression. These nucleotides are involved in gene silencing by controlling growth of amino acids into proteins (7). More than half of the DNA in our genome is made up of repeated protein sequences. Some of these appear to stabilize gene expression; others may have a role in spacing out the coding sequences so that they can be activated independently of other sequences. Some noncoding sequences enable our cells to produce different amounts of proteins at different times and can contain instructions to tell the cell how to switch genes on and off (9, 11, 13). Other noncoding sequences are part of genes, but don’t directly code for proteins. These are thought to help the cell to generate a number of different proteins from one gene (7, 16).

Epigenetics 2

Although miRNA are vital to normal cell function their mis-expression has been linked to several diseases, including cancer (5, 7, 9, 11, 13). miRNAs contribute to the epigenetic landscape as they can cause heritable changes in gene expression without altering the DNA sequences (5, 7, 16) miRNAs can both regulate and be regulated by methylation and histone modification creating ongoing mutations (5, 7, 11, 13, 16).

Altered expression of a number of noncoding RNA have been found in tumors and may play a role in the diagnosis of cancer and have been shown to be associated with response to chemotherapy (3, 4, 10, 13, 14, 16).

Recent advances in epigenetics offer a better understanding of underlying mechanisms of carcinogenesis and provide insight into the discovery of bio -markers for early detection, disease monitoring, prognosis and risk assessment.

 

References:
1) The Age, “Sins of the fathers and mothers”. Lifestyle. Thea O’Conner, Monday, January 20 2014
2) The Age, “You are what you mother ate”. Diet &Fitness. Thursday March 15, 2012
3) Dawson MA et al. Targeting epigenetic readers in cancer. N Engl J Med 2012, 367;7
4) Epigenetics as a Therapeutic Target in Breast Cancer. Journal of Mammary Gland Biology and Neoplasia, 2012; 17 (3-4): 191-204
5) Williams SCP. Epigenetics. Proceedings of the National Academy of Science. 2013, 110;9.

6) Ptshane M. Faddish Stuff: Epigenetics and the inheritance of Acquired Characteristics. FASEB Journal. 2013;27:1-2

7) Esteller M. Epigenetis in Cancer. N Eng J Med. 2008;358:1148-59

8) Ptshane M. Epigenetics: Core misconcept Proceedings of the National Academy of Science. 2013, 110;18:7101-7103

9) What is Epigenetic. Australian epigenetic alliance. wwwepialliance.org.au/contents/

10) Epigenetic Research – Garvan institute of Medical Research. www.garvan.org.au/research/cancer/epigenetics

11) Stein RA. Epigenetics – The Link Between Infectious Diseases and Cancer. JAMA 2011; 30514):1484-1485

12) Haitian L et al. Inflammation, a key event in cancer development. Mol CancerRes 2006;4(4):221-33

13) Kanwal, R Gupta S. Epigenetic modifications in cancer. Clinical Genetics.
2012; 81(4):303-311

14) Popiela AL et al. The meaning of the methylation of genomic DNA in the regulation of gene expression levels. Euro J of Genetics
15) Burdge, GC, et al

16) Kanwal R, Gupta S. Epigenetic an Cancer. J Appl Physiol, 2010:109: 598-605

17) Magnani L et al. ChIping away at breast cancer. Lancet Oncology, 2012: 13:12; 1185-7

18) Wang Y et al. Epigenetic inactivation of BRCA1 through promoter Hypermethylation in ovarian cancer progression. J Ob&G Research, 2013: 39:2; 549-554

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