This paper concerns the functional architecture of the cell nucleus. Though it is DNA that carries our literal blueprint, our ancestry includes the nucleus itself, passed down through the 2.5 billion year evolutionary history of the Eukarya. Nuclear structure is presented here as two contrasting possibilities. In one case, the nucleus is envisioned as being built upon a backbone of protein filaments, analogous to the cytoskeleton. In this conceptual framework, the chromosomes are considered to passively adopt locations that are dictated by their attachments to the imagined skeleton, 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 chromosomes themselves, and their activity. Here, gene activity is thought to be based on the binding of DNA sequence-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 the genes themselves, such as nascent mRNAs packaged into ribonucleoprotein particles as well as large, 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, prefabricated skeleton, 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, it is wise to keep an open mind. New advances in biophysical, nanotechnology and systems biology approaches to nuclear architecture encourage us to believe that we may soon graduate into the gymnasium - if not university, level of our nuclear education. Viewed metaphorically as art (as in the 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 expression canvas itself that we must now strive to know.
genome; nucleus; chromosomes; gene expression
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