Abstract 2600: Interaction of host cell factor-1 with the oncoprotein transcription factor MYC

Host cell factor (HCF)-1 is a highly-conserved epigenetic scaffolding protein that is essential for development, cell cycle progression, and cellular proliferation. Through integration into several chromatin modifying complexes, HCF-1 plays a critical role in regulating the activity of key transcription factors, such as the E2F family of proteins. HCF-1 is also linked to leukemogenesis, through its regulation by the BAP1 tumor suppressor and its incorporation into the oncogenic MLL complex. Despite its role in the cell cycle, presence at chromatin, and well-defined interactions, the function of HCF-1 in cancer remains under-studied and undetermined. Here we describe the role of HCF-1 in the context of its interaction with the transcription factor and oncoprotein MYC. MYC is overexpressed in most cancers and drives tumorigenesis by regulating the expression of genes involved in ribosome biogenesis, cell growth, and metabolism. The region of MYC responsible for interaction with HCF-1 is evolutionarily conserved in all vertebrate MYC family members, and we have previously demonstrated that mutations in MYC that selectively disable interaction with HCF-1 attenuate the tumorigenicity of MYC in vivo. This demonstrates that HCF-1 is an important co-factor for MYC-driven cancer. Using a battery of contemporary genomic approaches, including ChIP-seq, SLAM-seq, RNA-seq, and PRO-seq, coupled to a decisive CRISPR/Cas9 editing approach, we reveal the relationship of MYC and HCF-1 at chromatin and how this modulates the function of MYC as a transcription factor and oncoprotein. Citation Format: Tessa M. Popay, Lance R. Thomas, Jing Wang, Qi Liu, William P. Tansey. Interaction of host cell factor-1 with the oncoprotein transcription factor MYC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2600.