BAHD1, or bromo adjacent homology domain-containing protein 1, is a heterochromatinization factor. It is part of a multiprotein complex associated with histone deacetylases HDAC1/2. BAHD1 plays a role in chromatin-dependent gene regulation, and is involved in processes like heterochromatin formation and gene silencing [4]. It is associated with pathways related to nervous system development, behavior, metabolism, immunity, and cell proliferation [1,2]. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In male Bahd1 knockout mice, RNA sequencing showed about 2500 deregulated genes, mainly related to nervous system function, behavior, metabolism, and immunity. Bahd1 heterozygous male mice exhibited anxiety-like behavior and reduced prepulse inhibition [1]. In breast cancer cells, downregulation of BAHD1 induced cell cycle arrest in G1 phase, affecting proliferation, migration, and invasion [2]. In erythropoiesis, FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression [3]. Ablation of the Bahd1 gene in mice led to hypocholesterolemia, hypoglycemia, decreased body fat, placental growth restriction, and high neonatal mortality, along with altered expression of steroid/lipid metabolism genes [5]. A secreted listerial virulence factor could target BAHD1 to activate interferon-stimulated genes [6].

In conclusion, BAHD1 is crucial for chromatin-dependent gene regulation. Model-based research, especially KO mouse models, has revealed its significance in various biological processes. Its functions span across the nervous system, metabolism, cell proliferation, and immune response, suggesting its potential involvement in psychiatric disorders, breast cancer, hematopoietic development, placental development, and infectious diseases [1,2,3,5,6].

References:

1. Pourpre, Renaud, Naudon, Laurent, Meziane, Hamid, Herault, Yann, Bierne, Hélène. 2020. BAHD1 haploinsufficiency results in anxiety-like phenotypes in male mice. In PloS one, 15, e0232789. doi:10.1371/journal.pone.0232789. https://pubmed.ncbi.nlm.nih.gov/32407325/

2. Yang, Ze-Yu, Yin, Su-Peng, Ren, Qingnan, Zhang, Fan, Chen, Hongdan. 2022. BAHD1 serves as a critical regulator of breast cancer cell proliferation and invasion. In Breast cancer (Tokyo, Japan), 29, 516-530. doi:10.1007/s12282-022-01333-5. https://pubmed.ncbi.nlm.nih.gov/35048286/

3. Xu, Peng, Scott, Daniel C, Xu, Beisi, Schulman, Brenda A, Weiss, Mitchell J. . FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression in erythropoiesis. In Blood, 137, 155-167. doi:10.1182/blood.2020007809. https://pubmed.ncbi.nlm.nih.gov/33156908/

4. Bierne, Hélène, Tham, To Nam, Batsche, Eric, Feunteun, Jean, Cossart, Pascale. 2009. Human BAHD1 promotes heterochromatic gene silencing. In Proceedings of the National Academy of Sciences of the United States of America, 106, 13826-31. doi:10.1073/pnas.0901259106. https://pubmed.ncbi.nlm.nih.gov/19666599/

5. Lakisic, Goran, Lebreton, Alice, Pourpre, Renaud, Cossart, Pascale, Bierne, Hélène. 2016. Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism. In PLoS genetics, 12, e1005898. doi:10.1371/journal.pgen.1005898. https://pubmed.ncbi.nlm.nih.gov/26938916/

6. Lebreton, Alice, Lakisic, Goran, Job, Viviana, Cossart, Pascale, Bierne, Hélène. 2011. A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. In Science (New York, N.Y.), 331, 1319-21. doi:10.1126/science.1200120. https://pubmed.ncbi.nlm.nih.gov/21252314/