A key step in gene expression is transcription — the synthesis of RNA using genomic DNA as a template. A vast amount is known about the molecular factors which are central to transcription [1] and technology has advanced to a state where it is now routine to measure snapshots of the entire landscape of RNA transcripts with single-cell resolution [2,3]. Yet, our understanding of how transcription is causally orchestrated in both space and time is comparatively limited. Simply put, we lack biophysical models capable of quantitatively predicting how the local mechanical, dynamical, and biochemical environment determines transcriptional outputs in space and time throughout the nuclei of individual cells [4, 5, 6, 7, 8].
Our understanding of transcriptional dynamics largely results from detailed studies of the factors that influence the transcription of individual genes [9, 10, 11], with comparably few studies of the correlated transcriptional dynamics of multiple genes in the same nucleus at the same time. Active transcription of a gene typically involves long periods of quiescence interrupted by relatively shorter “bursts” of activity [9,12, 13, 14] (Figure 1). Since most work focuses on the behavior of single genes, one or a few at a time, it is unclear whether bursting in one part of the nucleus impacts bursting in another part (Figure 1b). Such spatial coordination of transcriptional bursting is expected because chromatin is an interconnected three-dimensional structure tied to transcription that evolves over time. Impressive progress has been made in developing models to explain the population level statistics of chromosome conformations [15, 16, 17], but the dynamics of chromosomal rearrangements in individual cells—which can include both local fluctuations [18,19] and nuclear-scale coherent motions [20]—remains comparatively poorly understood. Thus, any discussion of the prevalence and importance of chromosomal dynamics and transcriptional coordination is necessarily speculative. Nonetheless, as we describe below, there are indications that coordinated transcriptional bursting can occur.
Comments (0)