Intrinsically disordered regions (IDRs) are present in numerous proteins, yet their functions poorly understood. In C. elegans, SET-9 and SET-26 (orthologous to mammalian MLL5/KMT2E) are proteins with extensive IDRs and that function as readers of the H3K4me3 histone mark. Both proteins are expressed in the germline and have been previously shown to be involved in germline development and regulate expression of specific genes. However, the specific contribution of their IDRs to this process remains unclear. Here we show that by using CRISPR to precisely remove the N-terminal IDR from both SET-9, called SET-9(Δ N-IDR) or SET-26, called SET-26(Δ N-IDR) we observe a profound effect on fertility. Loss of the IDR from SET-9 caused severe infertility beginning at the F1 generation, whereas SET-26, exhibits a more gradual decline in fertility over successive generations. Notably the double mutants of SET-9(Δ N-IDR) and SET-26(Δ N-IDR) were completely infertile at the P0 generation and not able to be maintained. The deletion of the C-terminal IDR of both SET-9 and SET-26 proved to be inviable passed the P0 generation. This contrasts with established null mutants of each strain set-9(red8) and set-26(tm3526) which are known to be viable. One interesting finding to date points to the loss of IDP-1, a disordered protein that shares homology with SET-9/SET-26. Loss of IDP-1 rescues the fertility defect in SET-26(Δ N-IDR) but not SET-9(Δ N-IDR). This finding suggests that the IDRs of SET-9 and SET-26 are critical for their function in recognizing the H3K4me3 mark, potentially by modulating binding specificity or preventing aberrant interactions with other chromatin marks. Ongoing work to elucidate the mechanism of the N-terminal IDR will be presented in this poster.