Zcwpw2 is a paralog of ZCWPW1. Its CW domain can selectively recognize histone H3 trimethylated at Lys-4, similar to ZCWPW1 [2]. It is expected to be recruited to sites of PRDM9 binding and its tight co-evolution with PRDM9 across vertebrates suggests it is a key interactor, potentially playing a role in recruiting the recombination machinery or in double-strand break repair [1].

In a study on exercise response in obese individuals, Zcwpw2 was identified as a novel candidate gene by the LASSO approach, potentially related to the differential response to endurance exercise training in obese high and low responders [3]. In diabetic nephropathy, the ZCWPW2 risk genotype was associated with increased glycosylated hemoglobin [4]. In childhood cancer patients, Zcwpw2 was located in a duplicated genomic region and exhibited altered RNA expression after in vitro irradiation [5]. In prostate cancer cells, Zcwpw2 was among the mRNAs whose expression was regulated by the orphan nuclear receptor Esrrb and its ligand DY131, with DY131 acting as an antagonist for its expression [6].

In conclusion, Zcwpw2 has functions related to histone binding, and may be involved in processes such as DNA recombination and repair. Its associations with exercise response, diabetic nephropathy, childhood cancer, and prostate cancer suggest its importance in these disease-related biological processes. Studies on Zcwpw2 using genetic models could potentially further clarify its role in these conditions.

References:

1. Cavassim, Maria Izabel A, Baker, Zachary, Hoge, Carla, Schumer, Molly, Przeworski, Molly. . PRDM9 losses in vertebrates are coupled to those of paralogs ZCWPW1 and ZCWPW2. In Proceedings of the National Academy of Sciences of the United States of America, 119, . doi:10.1073/pnas.2114401119. https://pubmed.ncbi.nlm.nih.gov/35217607/

2. Liu, Yanli, Tempel, Wolfram, Zhang, Qi, Qin, Su, Min, Jinrong. 2016. Family-wide Characterization of Histone Binding Abilities of Human CW Domain-containing Proteins. In The Journal of biological chemistry, 291, 9000-13. doi:10.1074/jbc.M116.718973. https://pubmed.ncbi.nlm.nih.gov/26933034/

3. Kovac, Leona, Goj, Thomas, Ouni, Meriem, Weigert, Cora, Schürmann, Annette. . Skeletal Muscle Gene Expression Signatures of Obese High and Low Responders to Endurance Exercise Training. In The Journal of clinical endocrinology and metabolism, 109, 1318-1327. doi:10.1210/clinem/dgad677. https://pubmed.ncbi.nlm.nih.gov/37988600/

4. Lu, Xiao, Ma, Junjun, Guo, Lili, Wu, Wei, Li, Rongshan. 2023. Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy. In Frontiers in endocrinology, 14, 1264517. doi:10.3389/fendo.2023.1264517. https://pubmed.ncbi.nlm.nih.gov/38189041/

5. Danuta, Galetzka, Tobias, Müller, Marcus, Dittrich, Manuela, Marron, Heinz, Schmidberger. 2020. Molecular karyotyping and gene expression analysis in childhood cancer patients. In Journal of molecular medicine (Berlin, Germany), 98, 1107-1123. doi:10.1007/s00109-020-01937-4. https://pubmed.ncbi.nlm.nih.gov/32577795/

6. Lu, Yuan, Li, Jilong, Cheng, Jianlin, Lubahn, Dennis B. 2015. Messenger RNA profile analysis deciphers new Esrrb responsive genes in prostate cancer cells. In BMC molecular biology, 16, 21. doi:10.1186/s12867-015-0049-1. https://pubmed.ncbi.nlm.nih.gov/26627478/