SUMMARY
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.
KEY WORDS
genome; nucleus; chromosomes; gene expression
REFERENCES
Becker M, Baumann C, John S, Walker DA,
Vigneron M, McNally JG, Hager GL:
Dynamic behavior of transcription factors on a
natural promoter in living cells. EMBO Rep 3:1188-1194, 2002.
Callan HG, Lloyd L: Lambrush chromosomes
of crested newts Triturus cristatus (Laurentii).
Phil Trans Roy Soc Lond, Ser B, 243:135-219, 1960.
Daneholt B: Pre-mRNP particles: from gene to
nuclear pore. Curr Biol 9:R412-R415, 1999.
Davidson EH, McClay DR, Hood L: Regulatory
gene networks and the properties of the
developmental process. Proc Natl Acad Sci
USA 100:1475-1480, 2003.
Gall JG: Spread preparations of Xenopus germinal
vesicle contents. In Spector DL,
Goldman RD, Leinwand LA (eds.): Cells:
A Laboratory Manual, Cold Spring Harbor
Laboratory Press, Plainview NY, 52.51-52.54,
1998.
O'Brien TP, Bult CJ, Cremer C, Grunze M,
Knowles BB, Langowski J, McNally J,
Pederson T, Politz JC, Pombo A,
Schmahl G, Spatz J, von Driel R: Genome
function and nuclear architecture: from gene
expression to nanoscience. Genome Res 13:1029-1041, 2003.
Oegema, K, Marshall WF, Sedat JW, Alberts BM: Two proteins that cycle
asynchronously between centrosomes and
nuclear structures: Drosophila CP60 and CP190.
J Cell Sci 110:1573-1583, 1997.
Pederson T: Thinking about a nuclear matrix.
J Mol Biol 277:147-159, 1998.
Pederson T: Half a century of the nuclear matrix.
Mol Biol Cell 11:799-805, 2000a.
Pederson T: Diffusional transport within the
nucleus: a message in the medium. Nat Cell
Biol 2:E73-E74, 2000b.
Pederson T: Protein mobility within the nucleus-what
are the right moves? Cell 104:635-638, 2001.
Pederson T: Dynamics and genome-centricity of
interchromatin domains in the nucleus. Nat
Cell Biol 4:E287-E291, 2002.
Pederson T, Aebi U: Actin in the nucleus:
what form and what for? J Struct Biol 140:3-9, 2002.
Politz JC, Browne ES, Wolf DE, Pederson T:
Intranuclear diffusion and hybridization state of
oligonucleotides measured by fluorescence
correlation spectroscopy in living cells. Proc
Natl Acad Sci USA 95:6043-6048, 1998.
Politz, JC, Tuft RA, Pederson T, Singer RH:
Movement of nuclear poly(A) RNA throughout
the interchromatin space in living cells. Curr
Biol 9:285-291, 1999.
Politz, JC, Pederson T: Movement of mRNA
from transcription site to nuclear pores.
J Struct Biol 129:252-257, 2000.
Politz JC, Pombo A: Genomics meets
nanoscience: probing the genes and the cell
nucleus at 10-9 meters. Genome Biol 3:reports4007.1-reports4007.3, 2002.
Sass H, Pederson T: Transcription-dependent
localization of U1 and U2 small nuclear
ribonucleoproteins at major sites of gene
activity in polytene chromosomes. J Mol Biol
180:911-926, 1984.
Wasser M, Chia W: The EAST protein of
Drosophila controls an expandable nuclear
endoskeleton. Nat Cell Biol 2:268-275, 2000.
|
CITED
0
|