Mettl22-KO Mouse

Mettl22, short for Methyltransferase-like 22, is a member of the methyltransferase-like family. It functions as a non-histone lysine methyltransferase and is involved in various biological processes [2]. It has been implicated in stem cell development, especially in hematopoietic stem cell development, suggesting its importance in maintaining normal hematopoiesis [1,3].

In hematopoietic stem cell development, a functional genome-wide RNAi screen identified Mettl22 as one of the genes essential for the differentiation of embryonic stem cells into hematopoietic stem/progenitor cells in vitro. Validation in zebrafish further confirmed its necessity for HSPC development and for maintaining human HSCs [3]. Additionally, Mettl22 methylates the DNA/RNA-binding protein Kin17 on lysine 135, affecting Kin17's association with chromatin. Overexpression of Mettl22 in HEK 293 cells displaces Kin17 from chromatin to the cytoplasmic fraction, indicating a role in regulating chromatin association [2].

In conclusion, Mettl22 plays crucial roles in hematopoietic stem cell development and in regulating the association of the protein Kin17 with chromatin. The identification of its function in HSPC development through in vitro and in vivo models, like in zebrafish, contributes to understanding normal hematopoiesis and potentially related hematological disorders. Its role in chromatin-related regulation also provides insights into epigenetic mechanisms [2,3].

References:

1. Tooley, John G, Catlin, James P, Tooley, Christine E Schaner. 2022. METTLing in Stem Cell and Cancer Biology. In Stem cell reviews and reports, 19, 76-91. doi:10.1007/s12015-022-10444-7. https://pubmed.ncbi.nlm.nih.gov/36094754/

2. Cloutier, Philippe, Lavallée-Adam, Mathieu, Faubert, Denis, Blanchette, Mathieu, Coulombe, Benoit. 2013. Methylation of the DNA/RNA-binding protein Kin17 by METTL22 affects its association with chromatin. In Journal of proteomics, 100, 115-24. doi:10.1016/j.jprot.2013.10.008. https://pubmed.ncbi.nlm.nih.gov/24140279/

3. Han, Tianxu, Yang, Chao-Shun, Chang, Kung-Yen, Imam, Farhad B, Rana, Tariq M. 2016. Identification of novel genes and networks governing hematopoietic stem cell development. In EMBO reports, 17, 1814-1828. doi:. https://pubmed.ncbi.nlm.nih.gov/27797851/