Brd9, or Bromodomain-containing protein 9, is a subunit of the non-canonical BAF chromatin remodeling complex and a member of the bromodomain family IV. It plays a role in regulating gene transcription through epigenetic modification, recruiting the ncBAF complex to the promoter. Brd9 is involved in multiple biological pathways, such as the TGF-β/Activin/Nodal pathway, interferon-β signaling, and ribosome biogenesis, and is of great biological importance in processes like cell fate determination, self-renewal, and differentiation [4,5,6,8]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In myeloid lineage-specific Brd9-deficient mice, osteoclast lineage commitment and bone resorption were enhanced due to down-regulation of interferon-β signaling, revealing Brd9's role in suppressing osteoclastogenesis [1]. In Brd9-deficient hematopoietic stem cells, chromatin accessibility was increased, leading to myeloid lineage skewing and impaired B cell development, indicating its role in cell fate determination [2]. In pancreatic ductal adenocarcinoma, inhibition and genetic ablation of Brd9 in pancreatic cancer stem-like cells blocked self-renewal, invasiveness, and improved gemcitabine sensitivity [3]. In multiple myeloma, depleting Brd9 by genetic and pharmacologic approaches downregulated ribosome biogenesis genes, inhibited cell growth [6]. In HIF2αlow/− clear cell renal cell carcinoma, BRD9 knockdown or use of a selective antagonist suppressed cell growth [7]. In macrophages, inhibition of Brd9 led to reduction in interferon-stimulated genes [8].

In conclusion, Brd9 is crucial for regulating gene expression and participating in various biological processes. Model-based research, especially KO/CKO mouse models, has revealed its roles in bone diseases, hematological malignancies, pancreatic cancer, and other disease areas. Understanding Brd9's functions provides potential therapeutic targets for these diseases.