Genome architecture and the role of transcription

Abstract

During development or in response to environmental stimuli, eukaryotic genes change both their expression and position in 3D nuclear space. Then, is a gene transcribed because of its position, or is position determined by transcription? Are genes stochastically or deterministically engaged in transcription cycles? Recent results confirm that RNA polymerases and their transcription factors play central roles in genome organization, and that stochastic events can give rise to apparently deterministic expression. As is so often the case in biology, structure both determines function and is influenced by it.

Figure 1

From linear to 3D architecture. (a) Linear structure. Genes typically encode an enhancer/promoter module (dotted outline) where RNA polymerases (RNAPII) and transcription factors dock (NFκB here), exons, introns and a 3′ untranslated region (utr); they are often flanked by insulators. Exons are nucleosome-rich and marked by H3K27-dimethyl and/or H3K36-trimethyl; splice sites (GT/AG) are nucleosome-poor; after the poly(A) site nucleosome density rises again. (b) Enhancer–promoter interactions deployed in cis (to generate a local loop) or trans may stimulate transcription. (c) Gene loop. The 5′ and 3′ ends of an active gene are juxtaposed, and tied by RNA polymerase and/or transcription factors (TFIIB here). (d) Transcription factories (pink) are polymorphic structures to which transcription units on the same or different chromosomes (Chr) are bound through RNA polymerases or transcription factors. ‘Open’ chromatin is transcribed when promoters in it attach to the factory; ‘closed’ chromatin is remote from the factory and inert [38].

Figure 2

Temporal modes of gene expression. (a) Bursting. Genes may fire (stochastically) in tightly coordinate bursts, resulting in distinct peaks of mRNA (left); in non-bursting genes (e.g. constitutive), stochastic initiation yields more even mRNA levels (right). (b) Cycling. Different levels of agonist (left; blue < orange < red) affect the translocation frequency of the responding transcription factor (right). Cartoon: a cytoplasmic transcription factor (TF; purple) translocates to the nucleus in response to an agonist.