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Genes not still, they move

Md. Riajul Hossain
Every living cell, whether it is of animal or of plant origin, contains genes on their chromosomes inside the nucleus which is the heart of this basic unit of life. These arrays of genes are arranged on the chromosomes in such a way that they take positions in different places of the three dimensional space within the nucleus. Surprisingly, the genes can move! They are in a state of dynamism, so they are highly organized as well as very finely tuned at any given time and condition. The genes change their positions in response to the metabolic state of the cell and outside envi-
ronment and the activity and function of genes are highly influenced by this.
Although human genome sequencing helped us to move into a new era of molecular biology, yet only the sequence of information cannot help us move much further. Recent work took advantage of the genome-wide localization of molecular marks on chromosomes to analyze their linear distributions at different length scales. The genome cell biology aided by 3-D imaging technology has created the possibility for the analysis of the internal spatial organization of the chromosomes. It has revealed that there are preferred positions for the chromosomes according to
the level of activity of their genes and also they have suitable neighborhoods to interact with. Actually, each chromosome occupies a distinct, well defined area of the nucleus known as "chromosome territories". Although this term was used by Theodor Boveri, the experimental evidence came from two German brothers, Thomas and Christoph Cremer, when they developed a method for visualizing chromosome in a small region of the nucleus which was perfected few years later by the development of another method called chromosome painting. Researchers have found that the position of chromosomes seems to influence the switching on or off of the genes and the genes change their positions according to their level of activity keeping their active copies at the central region of the nucleus and the inactive ones at the periphery of the nucleus. This is because; the nuclear periphery is lined with heterochromatin, the highly condensed state of chromatin, where the genes remain inactive. The core of the nucleus is full of transcriptional activity with a large number of genes being transcribed together, was first proposed by the Oxford University scientist Peter Cook. The genome cell biologists have learned that the positioning of the genes has implications with the formation of diseases and even the chromosomal position changes during the normal embryonic development.
In case of stem cells, the genes are more or less active as they lack the large heterochromatin regions. After getting a signal, the nuclear structure changes with the formation of lamin proteins which sequester the inactive genes in the peripheral regions of the nucleus leaving the active genes in the core to have the sufficient access to the transcription factories.
The concept was further enhanced from the observation that chromosomal positioning has implications with translocations which ultimately might lead to cancer where the chromosomes fuse only with the nearby chromosomes. To reveal the question of what actually determines the
positioning of the genes and chromosomes, Tom Misteli suggests that the positioning of the chromosomes in the nucleus is self organizing where arrival of signal in the nucleus triggers chromatin remodeling and the inactive gene comes to the core from the periphery and gets access to the transcription factors and in this way the activity of the gene itself actually determines its position. With a better insight in this matter, hopefully, will enable early prediction of cancers and other diseases simply by observing the positioning of the genes and chromosomes in the cellular house they reside in.
The writer is a Lecturer in
Biotechnology at BRAC University.