An RB-Condensin II Complex Mediates Long-Range Chromosome Interactions and Influences Expression at Divergently Paired Genes

ABSTRACT

Interphase chromosomes are organized into topologically associated domains in order to establish and maintain integrity of transcriptional programs that remain poorly understood. Here, we show that condensin II and TFIIIC are recruited to bidirectionally transcribed promoters by a mechanism that is dependent on the retinoblastoma (RB) protein. Long-range chromosome contacts are disrupted by loss of condensin II loading, which leads to altered expression at bidirectional gene pairs. This study demonstrates that mammalian condensin II functions to organize long-range chromosome contacts and regulate transcription at specific genes. In addition, RB dependence of condensin II suggests that widespread misregulation of chromosome contacts and transcriptional alterations are a consequence of RB mutation.

KEYWORDS:

• condensin II
• TFIIIC
• epigenetics
• chromosome architecture
• gene expression
• retinoblastoma protein
• chromosome organization
• regulation of gene expression

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ACKNOWLEDGMENTS

We thank numerous colleagues for discussions and encouragement over the course of this study.

A.E.M. was a recipient of fellowship support from NSERC and OGS. This work was supported by funding from the CIHR (MOP 324579). F.A.D. is the Wolfe Senior Fellow in Tumor Suppressor Genes at Western University.

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.