A novel strategy of transcription regulation by intra-genic nucleosome ordering

Abstract

Numerous studies of chromatin structure showed that nucleosome free regions (NFRs) located at 5' gene ends contribute to transcription initiation regulation. Here, we determine the role of intragenic chromatin structure on gene expression regulation. We show that, along S. cerevisiae genes, nucleosomes are highly organized following two types of architecture that depend only on the distance between the NFRs located at the 5' and 3' gene ends. In the first type, this distance constraints in vivo the positioning of n nucleosomes regularly organized in a "crystal-like" array. In the second type, this distance is such that the corresponding genes can accomodate either n or (n+1) nucleosomes thereby displaying two possible "crystal-like" arrays of n weakly-compacted or n+1 highly-compacted nucleosomes. This adaptability confers "bi-stable" properties to chromatin and is a key to its dynamics. Compared to "crystal-like" genes, "bi-stable" genes present higher transcriptional plasticity, higher sensitivity to chromatin regulators, higher H3 turnover rate and lower H2A.Z enrichment. The results strongly suggest that transcription elongation is facilitated by higher chromatin compaction. The data allow us to propose a new paradigm of transcriptional control mediated by the stability and the level of compaction of the intragenic chromatin architecture and open new ways for investigating eukaryotic gene expression regulation.