Brd1-KO Mouse

Brd1, or bromodomain-containing protein 1, encodes an epigenetic regulator. It is an essential component of histone acetyltransferase (HAT) complexes, playing a crucial role in regulating gene transcription and modifying chromatin structures. It is involved in various biological processes such as brain development, lipid metabolism, and oxidative phosphorylation, and is associated with diseases like cancer and mental illnesses [1,2,3]. Genetic models, especially knockout mouse models, have been valuable in studying its functions.

In gastric cancer, NIT2 interacts with Brd1 to inhibit HBO1-mediated acetylation of histone H3 at lysine-14 (H3K14ac) and RELA-targeted oxidative phosphorylation (OXPHOS) gene expression. Depletion of NIT2 leads to Brd1 forming phase separation, increasing RELA stability and conferring 5-Fluorouracil resistance [1]. In hepatocellular carcinoma (HCC), BRD1 deficiency impedes HCC cell proliferation and metastasis by regulating H3K9ac/H3K9me3 transition, affecting SREBF1-related lipid metabolism [2]. In the brain, inactivation of Brd1 in mice causes failure-to-thrive, seizure susceptibility, along with abnormal histone H3 acetylation and N-tail clipping, suggesting Brd1 controls gene expression epigenetically [4].

In summary, Brd1 is a key epigenetic regulator involved in multiple biological processes. Model-based research, particularly KO mouse models, has revealed its significant roles in cancer and mental-related diseases. Understanding Brd1 provides insights into the epigenetic mechanisms underlying these diseases, potentially leading to new therapeutic strategies.

References:

1. Wang, Ziyang, Di, Yuqin, Wen, Xiangqiong, Wang, Xiongjun, He, Weiling. 2024. NIT2 dampens BRD1 phase separation and restrains oxidative phosphorylation to enhance chemosensitivity in gastric cancer. In Science translational medicine, 16, eado8333. doi:10.1126/scitranslmed.ado8333. https://pubmed.ncbi.nlm.nih.gov/39565874/

2. Zhang, Mingyang, Bai, Jing, Yuan, Hengye, Yan, Jia, Wang, Changshan. 2025. BRD1 deficiency affects SREBF1-related lipid metabolism through regulating H3K9ac/H3K9me3 transition to inhibit HCC progression. In Cell death & disease, 16, 104. doi:10.1038/s41419-025-07404-7. https://pubmed.ncbi.nlm.nih.gov/39962068/

3. Paternoster, Veerle, Cömert, Cagla, Kirk, Louise Sand, Børglum, Anders Dupont, Christensen, Jane Hvarregaard. 2022. The psychiatric risk gene BRD1 modulates mitochondrial bioenergetics by transcriptional regulation. In Translational psychiatry, 12, 319. doi:10.1038/s41398-022-02053-2. https://pubmed.ncbi.nlm.nih.gov/35941107/

4. Paternoster, Veerle, Edhager, Anders Valdemar, Qvist, Per, Palmfeldt, Johan, Christensen, Jane Hvarregaard. 2021. Inactivation of the Schizophrenia-associated BRD1 gene in Brain Causes Failure-to-thrive, Seizure Susceptibility and Abnormal Histone H3 Acetylation and N-tail Clipping. In Molecular neurobiology, 58, 4495-4505. doi:10.1007/s12035-021-02432-8. https://pubmed.ncbi.nlm.nih.gov/34056693/