Active genes dynamically colocalize to shared sites of ongoing transcription

Abstract

The intranuclear position of many genes has been correlated with their activity state, suggesting that migration to functional subcompartments may influence gene expression. Indeed, nascent RNA production and RNA polymerase II seem to be localized into discrete foci or 'transcription factories'. Current estimates from cultured cells indicate that multiple genes could occupy the same factory, although this has not yet been observed. Here we show that, during transcription in vivo, distal genes colocalize to the same transcription factory at high frequencies. Active genes are dynamically organized into shared nuclear subcompartments, and movement into or out of these factories results in activation or abatement of transcription. Thus, rather than recruiting and assembling transcription complexes, active genes migrate to preassembled transcription sites.The activity state of a gene can often be correlated with its intranuclear localization to specific subregions or its position relative to constitutive heterochromatin [1][2][3][4][5][6] ; however, it is unclear whether activation or repression of an individual gene is a cause or consequence of intranuclear position. Transcriptionally active genes have been proposed to associate with transcription factories, discrete nuclear sites of nascent RNA production and concentrated transcriptional components, such as RNA polymerase [7][8][9][10][11][12] . Calculations using the number of RNA polymerase II (RNAP II) transcription factories in HeLa cells (several thousand per nucleus) and estimates of the number of transcription units suggest that several active genes could occupy the same factory 10

The juxtaposition of a promoter with a locus control region transcriptional domain activates gene expression

“…The final chromatin conformation at the active locus places the hGH-N promoter in close proximity to the PolIIenriched LCR/CD79b transcriptional domain. This relocation of a promoter into an environment rich in elongating PolII is reminiscent of reports of close physical relationships between certain activated genes and PolII-enriched subnuclear 'transcriptional factories' (Iborra et al, 1996;Grande et al, 1997;Osborne et al, 2004;Ragoczy et al, 2006). Whether hGH-N gene activation is linked to an association with subnuclear transcription factories, or whether the juxtaposition of the promoter with the local accumulation of PolII within its LCR is sufficient will be of interest in future studies.…”

Human transcriptional interactome of chromatin contribute to gene co-expression

“…It was suggested that transcription active sites exist in nucleus, such as Pol II-enriched transcription factories [4] and splicing-factor-enriched speckles [7]. Genes locate on such sites are more actively transcribed, and could move in and out to be transcriptionally active or quiescent [4,16].…”

“…Genes locate on such sites are more actively transcribed, and could move in and out to be transcriptionally active or quiescent [4,16]. Such movement may be an important factor in gene transcription regulation [2,4,17]. In Hi-C experiment, formaldehyde is used to cross-link cells, resulting in covalent links between spatially adjacent chromatin segments [10].…”

“…Mechanisms such as transcription factory[4,5] and nucleus speckles[6-8], know as the "transcriptional interactome" were proposed, and spatial linkage of sequence-distant but function-related genes were revealed in case studies, although there are still debates on mechanisms [5,8]. Recently, the only "genome-wide study" was reported to demonstrate transcription interactions [5].…”

The Epigenetic Landscape of Lineage Choice: Lessons From the Heritability of Cd4 and Cd8 Expression

“…Rather, it is thought to be a dynamic process involving the movement of chromatin fibers to allow co-regulated genes to come together in the subnuclear space. Osborne et al (2004) found that active genes co-localize with reservoirs of active RNA polymerase II in what are termed "transcription factories". Subsequently, Spilianakis et al showed that genes on different chromosomes (the Il4 locus on chromosome 11 and Ifng on chromosome 10) could interact in a developmentally regulated manner and this interaction had a functional role in the expression of both loci, since deletion of a regulatory element on one chromosome could affect the expression of a locus on the other (2005).…”