Transcription of rRNA in early mouse embryos promotes chromatin reorganization and expression of major satellite repeats

Abstract

During the first cell cycles of the early development, the chromatin of the embryo is highly reprogrammed alongside that embryonic genome starts its own transcription. The spatial organization of the genome is a major process that contributes to regulating gene transcription in time and space, however, it is poorly studied in the context of early embryos. To study the cause and effect link between transcription and spatial organization in embryos, we focused on the ribosomal genes, that are first silent and begin to transcribe during the 2-cell stage in the mouse. We demonstrated that ribosomal sequences and early unprocessed rRNAs are spatially organized in a very peculiar manner from the 2-cell to the 16-cell. Using drugs interfering with ribosomal DNA transcription, we show that this organization, totally different from somatic cells, depends on an active transcription of ribosomal genes and induces a unique chromatin environment that favors transcription of major satellite sequences after the 4-cell stage.

Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells

“…These results also provide an interpretation for a previous observation that an unknown nuclear RNA component can sustain the higher-order structure of pericentric heterochromatin 53 , and presents evidence that the ability to maintain chromocenter stability resides at least in part with the transcript itself. Using RNA-FISH, we found that MSR transcripts in ESCs tend to localise close to the periphery of chromocenters, a pattern corroborated by recent studies 54 , 55 . As satellite repeats are under the transcriptional control of pluripotency factors in ESCs 15 , these findings provide a direct connection between cell state and heterochromatin regulation.…”

H3K27me3 at pericentromeric heterochromatin is a defining feature of the early mouse blastocyst

“…These sequences are packed in clusters of condensed chromatin called chromocenters, forming foci heavily stained by the nuclear dye DAPI 14 . During mouse development, the formation of chromocenters at the late 2-cell stage requires a mandatory transcription burst of major satellite sequences, which are then maintained at a low level of transcriptional activity 15 , 16 . Two studies have shown that chromocenters of ESCs are partially marked by H3K27me3, even though H3K27me3 is normally found at facultative heterochromatin 10 , 11 .…”