A biophysical model for transcription factories

Abstract

Transcription factories are nuclear domains where gene transcription takes placealthough the molecular basis for their formation and maintenance are unknown. In thisstudy, we explored how the properties of chromatin as a polymer may contribute to thestructure of transcription factories. We found that transcriptional active chromatincontains modifications like histone H4 acetylated at Lysine 16 (H4K16ac). Singlefibre analysis showed that this modification spans the entire body of the gene.Furthermore, H4K16ac genes cluster in regions up to 500 Kb alternating active andinactive chromatin. The introduction of H4K16ac in chromatin induces stiffness in thechromatin fibre. The result of this change in flexibility is that chromatin couldbehave like a multi-block copolymer with repetitions of stiff-flexible(active-inactive chromatin) components. Copolymers with such structure self-organizethrough spontaneous phase separation into microdomains. Consistent with such modelH4K16ac chromatin form foci that associates with nascent transcripts. We propose thattranscription factories are the result of the spontaneous concentration of H4K16acchromatin that are in proximity, mainly in cis.