Abstract 2098: Genome-wide comparison of PU.1 and Spi-B binding sites in a mouse B lymphoma cell line

Background. The E26-transformation-specific (ETS) transcription factor Spi-B is required for the survival of Activated B Cell-type Diffuse Large B Cell Lymphoma cell lines and is recurrently amplified in B cell lymphoma. The ETS transcription factor PU.1 is highly related to Spi-B. Both PU.1 and Spi-B are expressed in B lymphoma cell lines, and have been demonstrated to redundantly activate transcription of genes required for differentiation and function. We hypothesized that Spi-B and PU.1 occupy similar regions of chromatin within the genome of a B lymphoma cell line. Results. To compare binding regions of Spi-B and PU.1, murine WEHI-279 lymphoma cells were infected with retroviral vectors encoding 3XFLAG-tagged PU.1 or Spi-B. Anti-FLAG chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) was performed. Analysis for high-stringency enriched genomic regions demonstrated that PU.1 occupied 4528 regions and Spi-B occupied 3360 regions. 1900 of these regions exhibited at least 100 base pairs of overlap for both factors. Regions bound by Spi-B and PU.1 were frequently located within genes associated with immune response and activation of B cells. Motif-finding revealed that both transcription factors were predominantly located at the ETS core domain (GGAA), however, other unique motifs were identified when examining regions associated with only one of the two factors. Motifs associated with unique PU.1 binding included POU2F2, while unique motifs in the Spi-B regions contained a combined ETS-IRF motif. Conclusions. Our results suggest that complementary biological functions of PU.1 and Spi-B may be explained by their interaction with a similar set of regions in the genome of B lymphoma cells. However, sites uniquely occupied by PU.1 or Spi-B provide insight into their unique functions. Citation Format: Lauren A. Solomon, Stephen K.h. Li, Jan Piskorz, Li S. Xu, Rodney P. DeKoter. Genome-wide comparison of PU.1 and Spi-B binding sites in a mouse B lymphoma cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2098. doi:10.1158/1538-7445.AM2015-2098