4.8 Article

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

Journal

NUCLEIC ACIDS RESEARCH
Volume 49, Issue 14, Pages 8007-8023

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab587

Keywords

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Funding

  1. Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Japan Agency for Medical Research and Development (AMED)
  2. Fujita Health University
  3. KAKENHI grants from the Japan Society for the Promotion of Science (JSPS) [20K09632, 20H03223]
  4. PRESTO, JST
  5. Multidisciplinary Research Laboratory System of Osaka University
  6. Osaka University Program for the Support of Networking among Present and Future Researchers
  7. Grants-in-Aid for Scientific Research [20H03223, 20K09632] Funding Source: KAKEN

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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.
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.

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