LAUSR

Despite the great significance of the tumor suppressor Rb in cancer biology, the full spectrum of its binding pattern in human cells was yet to be established. Here, we report that rather than exclusively associating with E2F-bound promoters, chromatin-bound Rb associates with three distinct types of loci—E2F1-bound promoters, AP-1-bound enhancers, and CTCF-bound insulators. The binding pattern of Rb correlated with cohesin binding and chromatin accessibility in all three types of Rb-bound regions. When cells entered the S phase after the G1/S checkpoint, Rb redistributed from promoters to enhancers, leading to distinct transcriptional changes. These Rb-bound enhancers were cell-type-specific, in contrast to Rb-bound promoters that were constitutively present throughout most human cell types. Overall, our study provides a comprehensive view on the role of the tumor suppressor Rb, which has a well-preserved role in the G1 phase of regulating transcription at E2F1-bound promoters, while having a cell-type-specific role in the S phase when cells are determined to replicate. Citation Format: Hanjun Lee, Ioanna M. Gkotinakou, Ioannis Sanidas, Michael S. Lawrence, Nicholas J. Dyson. The non-canonical role of Rb in enhancers and insulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1420.