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E2F6 initiates stable epigenetic silencing of germline genes during embryonic development

ABSTRACT: In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes, however the molecular mechanisms of this specificity remain unclear. Here we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in vivo, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long term epigenetic silencing during mammalian development.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Embryonic Stem Cell

SUBMITTER: Johana Chicher

LAB HEAD: Michael Weber

PROVIDER: PXD023974 | Pride | 2021-04-22

REPOSITORIES: Pride

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			Action	DRS
	2019_S48_JVallet_E2F6HA_IP1_14-10_dil3.mgf	Mgf
	2019_S48_JVallet_E2F6HA_IP1_14-10_dil3.raw	Raw
	2019_S48_JVallet_E2F6HA_IP1_18-07_dil5.mgf	Mgf
	2019_S48_JVallet_E2F6HA_IP1_18-07_dil5.raw	Raw
	2019_S48_JVallet_E2F6HA_IP1_8-10_dil3.mgf	Mgf

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