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 chromatin structure modifications. It is involved in various biological processes, such as normal brain development, and is associated with pathways like oxidative phosphorylation, lipid metabolism, and mitochondrial bioenergetics [1-3]. Genetic models, like knockout (KO) mouse models, have been valuable in studying its functions.

In gastric cancer, depletion of NIT2 led to 5-fluorouracil (5-FU) resistance as reduced NIT2 protein resulted in Brd1 forming phase separation and binding to histone H3, increasing RELA-targeted oxidative phosphorylation gene expression [1]. In hepatocellular carcinoma (HCC), BRD1 deficiency impeded cell proliferation and metastasis by regulating H3K9ac/H3K9me3 transition, affecting SREBF1-related lipid metabolism [2]. In the context of mental illness, modulation of Brd1 expression in cell lines altered mitochondrial physiology, metabolism, and bioenergetics, and reduced Brd1 expression in female mice led to depression-like behaviors [3,4].

In conclusion, Brd1 is a key epigenetic regulator influencing multiple biological processes. KO/CKO mouse models have revealed its significance in diseases such as gastric cancer, HCC, and mental illnesses, highlighting its potential as a therapeutic target in these disease areas.