Gs. Stein et al., Implications for interrelationships between nuclear architecture and control of gene expression under microgravity conditions, FASEB J, 13, 1999, pp. S157-S166
Components of nuclear architecture ape functionally interrelated with contr
ol of gene expression. There is growing appreciation that multiple levels o
f nuclear organization integrate the regulatory cues that support activatio
n and suppression of genes as well as the processing of gene transcripts. T
he linear representation of genes and promoter elements provide the potenti
al for responsiveness to physiological regulatory signals. Parameters of ch
romatin structure and nucleosome organization support synergism between act
ivities at independent regulatory sequences and render promoter elements ac
cessible or refractory to transcription factors. Association of genes, tran
scription factors, and the machinery for transcript processing with the nuc
lear matrix facilitates fidelity of gene expression within the three-dimens
ional context of nuclear architecture. Mechanisms must be defined that coup
le nuclear morphology with enzymatic parameters of gene expression. The rec
ent characterization of factors that mediate chromatin remodeling and ident
ification of intranuclear targeting signals that direct transcription facto
rs to subnuclear domains where gene expression occurs link genetic and stru
ctural components of transcriptional control. Nuclear reorganization and ab
errant intranuclear trafficking of transcription factors for developmental
and tissue-specific control occurs in tumor cells and in neurological disor
ders. Compromises in nuclear structure-function interrelationships can occu
r as a consequence of microgravity-mediated perturbations in cellular archi
tecture.