Epigenesis is regulation of genes by biochemical factors. Genes may become temporarily or permanently active or inactive based on environmental and cellular chemical messages received by the nucleus and the genes that make up that nucleus. Here are some known ways this happens.
Epigenesis Epigenetic Effects Genes Chromatin and Histone and Repressor Regulatory Proteins
Genes are a deoxyribose-phosphate backbone or core with four different kinds of nitrogen bases: adenine, thymine, guanine and cytosine (see photo below).
Genes can be regulated or controlled by being either turned or switched on (active), or off (inactive). But how is this turning off or turning on of genes done?
Genes have special regulatory coded areas called operator and promoter regions. Certain special chemicals or molecules called "repressors" can attach to operator gene sites and turn the gene off. When the repressor molecule locates or "sits down" on specific nucleotide sequences in the operator region of the gene there is a molecular blockage of the promoter region. The promoter region can be unblocked when the repressor is removed from the operator and when this happens it permits or promotes the attachment of RNA polymerase at the gene start or beginning site. However, when the promoter gene region is blocked by the repressor, then the RNA polymerase cannot transcribe the gene and make a copy of the m-RNA (i.e., messenger RNA, the molecular instruction that specifies the amino acid sequence for the protein to be assembled at the ribosomal site).
Repressor proteins can be removed from operator sites by means of specific inducers. Inducers are usually specific chemicals or molecules that can interact with and inactivate a repressor protein. This action causes the repressor to be removed the gene operator site.
The tryptophan operon is an example of a gene-regulation system which has been thoroughly studied.
The Nucleosome and Genetic Regulation and Control by Topoisomerases
Another control mechanism of genes is clearly related to histone proteins – small, basic, positively-charged molecules that can interact with the negatively-charged regions of the DNA (genes). The chromatin is actually a chemical complex of DNA and protein.
The nucleosome is a defined chromosome region of 147 base pairs of DNA and 2 copies each of histones H2a, H2b, H3 and H4. This is the fundamental, basic structure or format of chromatin and this molecular architecture is related to aspects of epigenetic regulation. The repression by histones, the basic proteins, can be overcome with the aid of two classes of enzymes:
- topoisomerase I which alters chromatin structure via ATP-dependent chromatin remodeling
- topoisomerase II which causes covalent modification of histone proteins.
Both topoisomerases can relax positive or negative supercoils of DNA. Only topoisomerase I can reintroduce negative supercoils.
Both topoisomerases and their activities often are changed, altered or modified in cancer cells. Scientists can design and synthesize unique biochemicals which can be tested 'in vitro" and "in vitro" for activity that inhibits, inactivates or modifies these enzymes. This is another approach for potential cancer and degenerative disease control.
Ubiquitin-proteasome system (UPS) for Protein Breakdown, Regulation and Control
Cells regulate proteins and protein synthesis in other ways in health and disease. Another understanding of protein regulation which helps to explain aspects of certain diseases and cells is by processing proteins.
The ubiquitin-proteasome system (UPS) is among the best for study, analysis and experimentation of an important protein regulatory control systems. In the case of cancer activation of cells there is proteasome destruction of IkB inhibitor that promotes cancerous multiplication. Consider this sequence of events below and the diagram-photos below from the National Cancer Institute:
- Nuclear factor-kB is termed NF-kB and the protein and if it is permitted to enter the nucleus it is capable of activating up to 100 different genes in the human nucleus.
- NF-kB is present normally in the cell's cytoplasm and is it controlled and inactivated by a protein "Inhibitor of NF-kB", or "IkB". Therefore, the NF-kB activity is inhibited normally because of IkB binding and control of NF-kB.
- NF-kB may be activated when the inhibitor IkB is phosphorylated and this phosphorylation of IkB promotes ubiquitinylation and marks IkB for degradation by proteasomes.
- The proteasome degrades ubiquitinylated IkB and releases NF-kB which migrates from the cytoplasm across the nuclear membrane and into the cell's nucleus. NF-kB can induce activity of certain types of genes which enhance cell survival and encourage proliferation.
Sources
Hiscott, J. et al. 2001. "Hostile takeovers: viral appropriation of the NF-kB pathway." J Clin Invest. 107(2): 143–151. doi: 10.1172/JCI11918. Accessed 7 December, 2011 @ ncbi.nlm.nih.gov
National Cancer Institute. "Targeted Therapies for Multiple Myeloma Tutorial." Accessed 7 December, 2011 @ cancer.gov
Donald Reinhardt - Think, read, write & live well always. DJR has a PhD in Biology/Microbiology & is a Fellow & Diplomate, ASM Amer Acad Micro.
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