Chromatin organization and transcriptional regulation

Abstract

Cell type specific transcriptional regulation must be adhered to in order to maintain cell identity throughout the lifetime of an organism, yet it must be flexible enough to allow for responses to endogenous and exogenous stimuli. This regulation is mediated not only by molecular factors (e.g. cell type specific transcription factors, histone and DNA modifications), but also on the level of chromatin and genome organization. In this review we focus on recent findings that have contributed to our understanding of higher order chromatin structure and genome organization within the nucleus. We highlight new findings on the dynamic positioning of genes relative to each other, as well as to their chromosome territory and the nuclear lamina, and how the position of genes correlates with their transcriptional activity.

Figure 1

Chromatin organization in the mammalian nucleus. (A) Chromosomes are organized in chromosome territories. (B) Chromosome territories are comprised of fractal globules, and fractal globules from adjacent chromosome territories can interdigitate. (C) Chromatin fibers interact (i) within a fractal globule (frequent), (ii) between fractal globules of the same chromosome territory (rare), or between adjacent chromosome territories (very rare). (D) Chromatin may form a 30nm fiber with a zigzag, solenoid or polymer melt organization (see text). (E) Chromatin is resolved as a 10nm `beads on a string' fiber consisting of nucleosomes.

Figure 2

Transcriptional activity influences chromatin topology. (A) Transcriptional activation of a gene may precede its movement within the nucleus. (B) An inactive gene may get activated subsequent to its movement to a site that is favorable to transcriptional activation. (C) Transcriptional activation and gene movement may be independent of each other. Red, inactive gene; green, active gene.