While the data presented here suggest that loss of interactions between RNase H2 and ZMYM3/GTFII-I/CoREST/HDAC2/KDM1A may result in AGS pathology, and that these interactions may be co-ordinated by ZMYM3, the identification of these interactions raises the more fundamental question: why do they exist at all? Here, RCOR1 is linked to Aicardi-Goutieres syndrome.