Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression

Early Embryonic Establishment of Constitutive Heterochromatin Involves H3K14ac-mediated Recruitment of Eggless/SetDB1

“…The SUMOylated lysines of KAP1 are in turn recognized by the SIM of SetDB1, mediating its selective enrichment on retrotransposons (Fukuda and Shinkai, 2020). While the similar DNA-binding protein mediated recruitment of Eggless/SetDB1 is less understood in Drosophila , a pioneer factor GAF that can specifically binds to GA repeats, is required for the establishment of constitutive heterochromatin on AAGAG satellite sequences (Gaskill et al ., 2023). How GAF interacts with Eggless/SetDB1 remains unclear.…”

“…Functional analyses have revealed that the known Eggless/SetDB1 recruitment mechanisms only guide heterochromatin formation on a small portion of repetitive elements (Fabry et al ., 2021; Gaskill et al ., 2023). Our study reports a new mode of Eggless/SetDB1 recruitment, in which the active histone modification H3K14ac can directly attract Eggless/SetDB1 via its N-terminal 3TD domain.…”

“…Different repetitive DNA elements seem to take on distinct molecular pathways to arrive at a heterochromatic state. Tandem AAGAG repeat relies on specific recognition by the pioneer factor GAF to initiate H3K9me3 deposition and transcriptional silencing (Gaskill et al, 2023). Some transposable elements, however, utilize piRNA-directed mechanism to engage Piwi and the PICTS complex with the nascent transposon transcripts to recruit Eggless/SetDB1 and instruct local heterochromatin formation in the early embryos (Batki et al, 2019; Fabry et al, 2021; Mugat et al, 2020; Ninova et al, 2020b; Zhao et al, 2019).…”

“…Besides, the emergence of heterochromatic features on different repetitive DNA elements is heterochronic. A group of tandem repetitive elements such as the 359-bp and AAGAG repeats attain H3K9me3 decoration and HP1a accumulation at the MBT, preceding other repeats (Gaskill et al ., 2023; Yuan and O’Farrell, 2016). To date, our understanding of the molecular basis underlying the precise recruitment of Eggless/SetDB1 and hence the inheritance of constitutive heterochromatic states across generations is far from complete.…”