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The homeobox transcription factor DUXBL controls exit from totipotency

ABSTRACT: In mice, exit from the totipotent 2-cell (2C) embryo stage requires silencing of the 2C-associated transcriptional program. However, the molecular mechanisms involved in this process remain poorly understood. Here, we demonstrate that the 2C-specific transcription factor DUX mediates an essential negative feedback loop by inducing the expression of DUXBL to promote this silencing.We show that DUXBL gains accessibility to DUX-bound regions specifically upon DUX expression.Furthermore, we determine that DUXBL interacts with TRIM24 and TRIM33, members of the tripartite motif superfamily involved in gene silencing and co-localizes with them in nuclear foci upon DUX expression. Importantly, DUXBL overexpression impairs 2C-associated transcription, whereas Duxbl inactivation in ESC increases DUX-dependent induction of the 2C-transcriptional program. Consequently, DUXBL deficiency in embryos results in sustained expression of 2C-associated transcripts, leading to early developmental arrest.Our study identifies DUXBL as an essential regulator of totipotency exit enabling the first divergence of cell fates.

ORGANISM(S): Mus musculus

PROVIDER: GSE234053 | GEO | 2023/12/07

REPOSITORIES: GEO

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The homeobox transcription factor DUXBL controls exit from the totipotent 2C state [RNA-seq]

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