Nuclear impressionism: how the active genome creates the very canvas on which gene expression is painted
Titel:
Nuclear impressionism: how the active genome creates the very canvas on which gene expression is painted
Auteur:
Thoru Pederson
Verschenen in:
Journal of applied biomedicine
Paginering:
Jaargang 1 (2003) nr. 3 pagina's 113-116
Jaar:
2003
Inhoud:
This paper concerns the functional architecture of the cell nucleus. Though it is DNA that carriesour literal blueprint, our ancestry includes the nucleus itself, passed down through the 2.5 billionyear evolutionary history of the Eukarya. Nuclear structure is presented here as two contrastingpossibilities. In one case, the nucleus is envisioned as being built upon a backbone of proteinfilaments, analogous to the cytoskeleton. In this conceptual framework, the chromosomes areconsidered to passively adopt locations that are dictated by their attachments to the imaginedskeleton, and their activity is postulated to be the result of such attachments. In the other case,nothing in the architectural design of the nucleus is more deterministic than the chromosomesthemselves, and their activity. Here, gene activity is thought to be based on the binding of DNAsequence-specific activator or silencing proteins that arrive at their target sites by diffusion.Moreover, additional elements of nuclear structure are viewed as arising from the very action of thegenes themselves, such as nascent mRNAs packaged into ribonucleoprotein particles as well aslarge, heterotypic molecular machines involved in RNA processing. In this case, termed the“genome-centric model”, the observed structure of the nucleus is not based on some underlying, prefabricatedskeleton, but is in fact the actual ongoing cytological manifestation of genes in action.Upon careful analysis of all the evidence, the genome-centric model enjoys favor at the present time.However, we are still in kindergarten days in our understanding of the cell nucleus and, as always, itis wise to keep an open mind. New advances in biophysical, nanotechnology and systems biologyapproaches to nuclear architecture encourage us to believe that we may soon graduate into thegymnasium – if not university, level of our nuclear education. Viewed metaphorically as art (as inthe playful title of this paper), we understand the paint at every atom of pigment on the palette –i.e., the covalent genome, the DNA. It is the final, creative work as applied to the gene expressioncanvas itself that we must now strive to know.