Abstract 4751: The function of bromodomain containing protein 4 (BRD44) in hematopoiesis

Abstract

Abstract Bromodomain containing protein 4 (BRD4) is an epigenetic transcription regulator that reads acetylated chromatin and is involved in the recruitment of transcriptional factors to initiate gene transcription. BRD4 is functionally versatile and has extensively been studied for its role in cell cycle progression, gene transcription regulation, chromatin organization and remodeling, as well as DNA replication and repair. In addition, BRD4 has been implicated in many solid and liquid tumors, and its inhibition shows promising preclinical activity, especially in hematopoietic malignancies. BRD4 is overexpressed in Leukemia and has been reported to play a role in hematopoietic stem cell expansion and progenitor development. However, the mechanisms of BRD4 in hematopoietic stem cell functions and disease development remain poorly understood. Using BRD44 knockout (BRD44 Δ/Δ, driven by Mx1 Cre to delete BRD44 in hematopoietic system) mouse model, we found that BRD4 is required for HSCs self-renewal and the loss of BRD44 impaired erythroid differentiation and skewed myeloid differentiation. BRD44 Δ/Δ HSPCs showed G0/G1 arrest, decreased S-phase, and increased senescence compared to wild type (WT) HSPCs. Our study demonstrates that BRD4 is essential for normal hematopoiesis. To further investigate the role of BRD4 in hematopoiesis, we generated BRD44 transgenic mice (driven by Vav1 promoter, to assure all BRD44 transgene expression is instructed in the hematopoietic system). Ongoing studies focus on determining the impact of BRD4 overexpression on hematopoietic stem cell functions. Citation Format: Francine Nihozeko. The function of bromodomain containing protein 4 (BRD44) in hematopoiesis. [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 4751.