Bahcc1, or Bromo-adjacent homology domain and coiled-coil containing 1, is a gene with significant roles in multiple biological processes. It encodes a protein that can act as a reader molecule of trimethylated histone H3 lysine 27 (H3K27me3), which is involved in regulating gene repression, cell-fate determination, and differentiation [3,4]. It also participates in various cellular pathways such as cell-cycle regulation, DNA repair, and epigenetic regulation, thereby being of great biological importance. Genetic models, especially mouse models, have been crucial in understanding its functions.

In melanoma, super-enhancer-driven expression of BAHCC1 promotes cell proliferation and genome stability. BAHCC1 silencing leads to decreased cell proliferation and delayed DNA repair, and its deficiency can cooperate with PARP inhibition to induce melanoma cell death [1]. In a mouse model of MLL-ENL-mediated leukemia, Bahcc1 is critical for the aberrant epigenetic program. MLL-ENL upregulates Bahcc1, and depletion of Bahcc1 in mice suppresses the leukemogenic activity of MLL-ENL [2]. Also, disruption of the BAHCC1-H3K27me3 interaction in leukemia causes derepression of H3K27me3-targeted genes involved in tumor suppression and cell differentiation, suppressing oncogenesis. In mice, a germline mutation at Bahcc1 to disrupt its H3K27me3 engagement causes partial postnatal lethality, indicating its role in development [3].

In summary, Bahcc1 plays essential roles in regulating cell-cycle, DNA repair, and epigenetic modification processes. Through gene knockout or conditional knockout mouse models, its significance in diseases such as melanoma and leukemia has been revealed. These findings contribute to understanding the biological functions of Bahcc1 and provide potential therapeutic targets for related diseases.

References:

1. Berico, Pietro, Nogaret, Maguelone, Cigrang, Max, Davidson, Irwin, Coin, Frédéric. 2023. Super-enhancer-driven expression of BAHCC1 promotes melanoma cell proliferation and genome stability. In Cell reports, 42, 113363. doi:10.1016/j.celrep.2023.113363. https://pubmed.ncbi.nlm.nih.gov/37924516/

2. Nakamura, Akihide, Masuya, Masahiro, Shinmei, Makoto, Nosaka, Tetsuya, Ono, Ryoichi. . Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL-mediated leukemia. In Blood advances, 8, 2193-2206. doi:10.1182/bloodadvances.2023011320. https://pubmed.ncbi.nlm.nih.gov/38452334/

3. Fan, Huitao, Lu, Jiuwei, Guo, Yiran, Song, Jikui, Wang, Gang Greg. 2020. BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis. In Nature genetics, 52, 1384-1396. doi:10.1038/s41588-020-00729-3. https://pubmed.ncbi.nlm.nih.gov/33139953/

4. Guo, Yiran, Zhao, Shuai, Wang, Gang Greg. 2021. Polycomb Gene Silencing Mechanisms: PRC2 Chromatin Targeting, H3K27me3 'Readout', and Phase Separation-Based Compaction. In Trends in genetics : TIG, 37, 547-565. doi:10.1016/j.tig.2020.12.006. https://pubmed.ncbi.nlm.nih.gov/33494958/