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Gene Silencing at the Nuclear Periphery - Essay Example

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The word "epigenetics" was coined by Conrad Waddington (1905-75) in the 1940s. (Holliday, 2006). Epigenetics (Latin: epi=above, over, outside, beside) refers to the modifications to DNA that persist from one cell division to the next, even though the underlying DNA sequence remains unaltered…
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Gene Silencing at the Nuclear Periphery
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Download file to see previous pages Some epigenetic abnormalities have been identified in human tumors, offering tremendous scope for epigenetic modulation as part of cancer chemotherapy. (TY Kim, YJ Bang, KD Robertson, 2006)
Histones are small, basic proteins which bind to DNA, to form nucleoproteins - this helps the DNA to be packed tightly into coiled coils. Histones are rich in the amino acids arginine and lysine. Unlike most proteins, histones are water soluble. The functions of histones include packing nucleoproteins for compaction, and chromatin regulation. Histones undergo modifications; this set of modifications which are interdependent and responsible for controlling gene activity is called the "Histone code". The histone code theory of gene regulation was articulated by David Allis and colleagues. According to this theory, expression of certain regions of DNA is turned on and off by histone code. Histone proteins are one of the most highly conserved proteins in eukaryotes, emphasizing their importance in cell biology.
Heterochromatin is the condensed, dense form of chromatin, which is transcriptionally inactive; hence it is peripherally located. It is abundantly seen in resting or reserve cells. It stains deeply during interphase (resting stage). The heterochromatin part of a chromosome either lacks genes or has repressed genes. Heterochromatin is seen in both pro and eukaryotes.
Euchromatin is delicate, thread-like, active form of chromatin. It is abundant in active, transcribing cells. The importance of euchromatin is because the portion of the DNA coil intended for transcription must uncoil, to permit reading of the code. It stains lightly and its gene concentration is high. It is usually under active transcription and hence it is partially or fully uncoiled. Prokaryotes have only euchromatin.
NUCLEAR LOCALISATION - ROLE IN GENE EXPRESSION
The vital facts about gene silencing are: (Shaklai et al, 2007)
1. Chromosomes rich in genes are centrally located in the nucleus. Conversely, gene poor ones are located in the periphery.
2. Inactive genes are silenced and translocated to the periphery.
3. If chromatin is moved to the periphery, it is silenced and rendered inactive.
Gene silencing plays an important role in determining the fate of different cell lines during development and defining their temporal order. (Fischer, Merkenschlager 2002)
cDNA MICROARRAY TECHNIQUE
cDNA microarray (c -complimentary) is a tool which helps us analyze and measure the activity of genes. This is done using the process of molecular hybridization. Adenine and thymine are complimentary; Guanine and cytosine are complimentary. While studying two pieces of DNA, if they hybridize (bind to one another), then we can conclude they are complimentary strands - opposite strands of a single gene. Conversely, if they do not hybridize, then they are unrelated.
Microarray expression technique has many applications - Gene expression profiling (comparing gene expressions in normal and abnormal cells), study of multigenic diseases like Parkinson's disease,detection of ...Download file to see next pagesRead More
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