Local states of chromatin compaction at transcription start sites control transcription levels

The 'open' and 'compact' regions of chromatin are considered to be regions of active and silent transcription, respectively. However, individual genes produce transcripts at different levels, suggesting that transcription output does not depend on the simple open-compact conversion of chromatin, but on structural variations in chromatin itself, which so far have remained elusive. In this study, weakly crosslinked chromatin was subjected to sedimentation velocity centrifugation, which fractionated the chromatin according to its degree of compaction. Open chromatin remained in upper fractions, while compact chromatin sedimented to lower fractions depending on the level of nucleosome assembly. Although nucleosomes were evenly detected in all fractions, histone Hi was more highly enriched in the lower fractions. H1 was found to self-associate and crosslinked to histone H3, suggesting that HI bound to H3 interacts with another H I in an adjacent nucleosome to form compact chromatin. Genome-wide analyses revealed that nearly the entire genome consists of compact chromatin without differences in compaction between repeat and non-repeat sequences; however, active transcription start sites (TSSs) were rarely found in compact chromatin. Considering the inverse correlation between chromatin compaction and RNA polymerase binding at TSSs, it appears that local states of chromatin compaction determine transcription levels.

Automated summary

The 'open' and 'compact' regions of chromatin are implicated in active and silent transcription, respectively. However, this study suggests that transcription output is not only determined by the open-compact conversion of chromatin, but also by structural variations within chromatin itself. It was found that chromatin compaction plays a crucial role in transcription levels, with local states of chromatin compaction determining gene expression.