BRD3 (bromodomain-containing 3) is a protein-coding gene that belongs to the bromodomain and extra-terminal (BET) protein family, which also includes BRD2, BRD4, and BRDT. These proteins are characterized by the presence of two bromodomains and an extra-terminal (ET) domain, which enables them to recognize and bind to acetylated lysine residues on histone tails, thereby affecting chromatin structure and gene expression. BRD3 has been identified as a key player in the regulation of gene transcription. By binding to acetylated histones, BRD3 can recruit the transcriptional machinery to specific genomic regions, thereby promoting the transcription of certain genes. This regulatory function makes BRD3 an essential component of cellular processes such as cell signaling, growth, and differentiation.
Multiple studies have implicated BRD3 in various human diseases, most notably cancer. For example, BRD3 was found to form a fusion protein with the NUT gene (NUTM1), resulting in a malignant cancer called NUT midline carcinoma (NMC). This particular type of cancer is characterized by rapid and uncontrolled growth of cancer cells, often affecting midline structures such as the head, neck, and mediastinum. BRD3-NUT fusion proteins are thought to drive carcinogenesis by aberrantly maintaining chromatin in a hyperacetylated state, which in turn leads to uncontrolled gene expression and cell proliferation.
Creating a BRD3 knockout (KO) in the 293T cell line provides a powerful tool for studying the biological functions of BRD3 and its involvement in various cellular processes. Here are a few key applications of the BRD3 KO 293T cell line:
Gene Regulation Studies: BRD3 interacts with acetylated lysines on histone tails to influence gene expression patterns. The BRD3 KO 293T cell line can be used to study changes in gene expression by comparing the transcriptomes of wild-type and BRD3-deficient cells.
Cancer Research: The BET family of proteins, including BRD3, has been implicated in various cancers. The BRD3 KO 293T cell line can be used to understand the role of BRD3 in cancer cell proliferation, apoptosis, and metastasis.
Drug Screening and Development: By comparing the responses of wild-type and BRD3-deficient cells to various compounds, researchers can identify specific inhibitors of BRD3 and evaluate their therapeutic potential. This cell line can also be used to determine the specificity and efficacy of BET inhibitors and to study off-target effects of drugs targeting the BET family.
Epigenetic Regulation: As a member of the BET family, BRD3 plays an important role in epigenetic regulation of gene expression. Using the BRD3 KO 293T cell line, researchers can study the effects of BRD3 loss on the epigenetic landscape of cells.
Stem Cell Research: BRD3 has been implicated in the maintenance of stem cell pluripotency and differentiation. The BRD3 KO 293T cell line can be used to study the role of BRD3 in stem cell biology, including self-renewal and differentiation processes.