Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions

Abstract

In recent years there has been considerable and growing interest in the 3-dimensional organization of genomes. In this manuscript we present an integrated computational-molecular study that produces an ensemble of high-resolution 3-dimensional conformations of the budding yeast genome. The compaction, folding and spatial organization of the chromosomes was based on empirical data determined using proximity-based ligation. Our models incorporate external constraints that allow the separation of gross organizational effects from those due to local interactions. Our models show that yeast chromosomes have preferred yet non-exclusive positions. They also identify interaction dependent clustering of tRNAs, early firing origins of replication, and Gal4 protein binding sites, yet the cluster composition is dynamic. Our results support a link between structure and transcription that occurs within the context of a flexible genome organization.

Keywords: :

• yeast
• genome architecture
• proximity-based ligation
• modeling

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

JOS acknowledges support from the Auckland Medical Research Foundation, Massey University Research Fund and Marsden Fund. LRG was supported by a Swiss National Science Foundation fellowship (PBBSP3–130910). CR was funded by an HRC Ph.D. scholarship (08/554). JL acknowledges support by a collaboration grant from the German Federal Ministry of Education and Research. The authors thank Susan Gasser for her advice and support.

Supplemental Material

Supplemental material can be found at:

www.landesbioscience.com/journals/nucleus/article/20971

Notes

† These authors contributed equally to this work.