Extended Data Fig. 10: RNA-dependent heterochromatin formation models.

a, RNA-dependent heterochromatin formation on IAPEz-int in mES cells. Specifically, METTL3 and other m⁶A methyltransferase components methylate IAPEz transcripts, which are recognized by the m⁶A reader protein YTHDC1. YTHDC1 in turn stabilizes METTL3 binding, possibly through protein–protein interactions. Chromatin-associated METTL3 enhances SETDB1–TRIM28 binding, which in turn stabilizes METTL3 recruitment. b, RNA-dependent heterochromatin formation on centromere regions in S. pombe. Specifically, heterochromatin generation over centromere regions is initiated by the base-paring recognition and binding of the RITS complex to RNAs transcribed from these regions, which in turn enhances sRNA generation through recruitment of RDRC. RITS then recruits CLRC to catalyse H3K9 methylation, which in turn promotes RITS binding. c, RNA-dependent heterochromatin formation on DSR genes in S. pombe. Specifically, Mmi1 protein recognizes the DSR consensus motif on RNAs transcribed from these genes and then recruits the H3K9 methyltransferase Clr4 through Red1.