Supplementary Figure 8: A model of Trabid function in TLR-mediated induction of Il12b. | Nature Immunology

Supplementary Figure 8: A model of Trabid function in TLR-mediated induction of Il12b.

From: Epigenetic regulation of the expression of Il12 and Il23 and autoimmune inflammation by the deubiquitinase Trabid

Supplementary Figure 8

LPS induces the expression of the Jmjd2d gene (Kdm4d) via an unknown signaling pathway. Jmjd2d mediates removal of H3K9me2 and H3K9me3 from the Il12b promoter, thereby promoting c-Rel binding to the κB element and induction of Il12b expression. The fate of Jmjd2d in TLR-stimulated DCs is tightly controlled by ubiquitination. An unknown E3 ubiquitin ligase mediates Jmjd2d ubiquitination and degradation, whereas Trabid deubiquitinates Jmjd2d to prevent its degradation. Trabid deficiency causes elevated ubiquitination and degradation of Jmjd2d and, thus, reduces the level of Il12b induction. Similar mechanisms may apply to the induction of Il12a and Il23a genes.

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