Fig. 6.

Illustration of the progression of Set1 knockdown phenotypes in adult testis. (A) In a wild-type testis, H3K4me3 is present in all cell types of the testis, but for simplicity the presence of H3K4me3 (dark green) is only shown in the germ cells, including GSCs (bright green), gonialblasts and spermatogonia (light green). CySCs are shown in magenta, cyst cells in pink, and hub cells in blue. (B) Knockdown of Set1 in the early germline results in a reduction of H3K4me3 in GSCs, gonialblasts and spermatogonia. (C) The phenotypes at the earlier time points include a reduction of germ cells and cyst cells. (D) The phenotypes at the later time points include overpopulated early-stage germ cells ectopically expressing Stat92E and Mad, as well as increased hub size. (E) Putative pathways of Set1 function in the early-stage germline, including GSCs. Given that both Stat92E and Mad have increased expression in the Set1 KD testes, they are likely indirect targets of Set1. One possible explanation is that Set1 directly regulates inhibitors of both Stat92E and Mad (left). Compromising Set1 could lead to the downregulation of these inhibitors and ectopic expression of Stat92E and Mad, resulting in the GSC loss and early-stage germ cell overproliferation phenotypes (right).