Mbd3l2, a protein-coding gene, is homologous to MBD2 and MBD3 but lacks the methyl-CpG-binding domain [2,4]. It is involved in epigenetic regulation and transcriptional modulation. Mbd3l2 can interact with MBD3 and components of the NuRD complex, and may play a role in processes related to DNA methylation-mediated gene silencing and activation [2].

Knockout mouse models of Mbd3l2 were created to study its function. Mbd3l2 knockout mice were viable and fertile, suggesting that Mbd3l2 is dispensable for early development, fertility, and zygotic DNA demethylation in the mouse [3].

In summary, while Mbd3l2-knockout mouse models indicate that it is not essential for early development and zygotic DNA demethylation, it still plays important roles in epigenetic regulation, such as modulating Tet2 enzymatic activity in 5-methylcytosine oxidation, and interacting with components of the NuRD complex to potentially reactivate transcription from methylated DNA [1,2]. These functions are relevant for understanding epigenetic-related disease mechanisms like malignancies [1].

References:

1. Peng, Lina, Li, Yan, Xi, Yanping, Wu, Feizhen, Yu, Wenqiang. 2016. MBD3L2 promotes Tet2 enzymatic activity for mediating 5-methylcytosine oxidation. In Journal of cell science, 129, 1059-71. doi:10.1242/jcs.179044. https://pubmed.ncbi.nlm.nih.gov/26769901/

2. Jin, Seung-Gi, Jiang, Chun-Ling, Rauch, Tibor, Li, Hongwei, Pfeifer, Gerd P. 2005. MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing. In The Journal of biological chemistry, 280, 12700-9. doi:. https://pubmed.ncbi.nlm.nih.gov/15701600/

3. Jin, Seung-Gi, Tsark, Walter, Szabó, Piroska E, Pfeifer, Gerd P. . Haploid male germ cell- and oocyte-specific Mbd3l1 and Mbd3l2 genes are dispensable for early development, fertility, and zygotic DNA demethylation in the mouse. In Developmental dynamics : an official publication of the American Association of Anatomists, 237, 3435-43. doi:10.1002/dvdy.21767. https://pubmed.ncbi.nlm.nih.gov/18942147/

4. Jiang, Chun Ling, Jin, Seung Gi, Lee, Dong Hyun, Cooney, Austin J, Pfeifer, Gerd P. . MBD3L1 and MBD3L2, two new proteins homologous to the methyl-CpG-binding proteins MBD2 and MBD3: characterization of MBD3L1 as a testis-specific transcriptional repressor. In Genomics, 80, 621-9. doi:. https://pubmed.ncbi.nlm.nih.gov/12504854/