Atoh1 is repurposed from neuronal to hair cell determinant by Gfi1 acting as a coactivator without redistribution of its genomic binding sites
Costa, A.; Powell, L. M.; Soufi, A.; Lowell, S.; Jarman, A. P.
Show abstract
Although the lineage-determining ability of transcription factors is often modulated according to cellular context, the mechanisms by which such switching occurs are not well known. Using a transcriptional programming model, we found that Atoh1 is repurposed from a neuronal to an inner ear hair cell (HC) determinant by the combined activities of Gfi1 and Pou4f3. In this process, Atoh1 maintains its regulation of neuronal genes but gains ability to regulate HC genes. Pou4f3 enables Atoh1 access to genomic locations controlling the expression of sensory (including HC) genes, but Atoh1+Pou4f3 are not sufficient for HC differentiation. Gfi1 is key to the Atoh1-induced lineage switch, but surprisingly does not alter Atoh1s binding profile. Gfi1 acts in two divergent ways. It represses the induction by Atoh1 of genes that antagonise HC differentiation, a function in keeping with its well-known repressor role in haematopoiesis. Remarkably, we find that Gfi1 also acts as a co-activator: it binds directly to Atoh1 at existing target genes to enhance its activity. These findings highlight the diversity of mechanisms by which one TF can redirect the activity of another to enable combinatorial control of cell identity.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Mechanisms Underlying WNT-mediated Priming of Human Embryonic Stem Cells 96%
- Dissecting Hes-centered transcriptional networks in neural stem cell maintenance and tumorigenesis in Drosophila 95%
- Hox binding specificity is directed by DNA sequence preferences and differential abilities to engage inaccessible chromatin. 95%
Similar papers in this journal
Similar papers in this journal
- Rapid redistribution and extensive binding of NANOG and GATA6 at shared regulatory elements underlie specification of divergent cell fates 96%
- Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development 95%
- Epigenetic regulations follow cell cycle progression during differentiation of human pluripotent stem cells. 95%
Similar papers in this journal
- PRC2 Promotes Canalisation during Endodermal Differentiation 96%
- Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage 94%
- Ush regulates hemocyte-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis 94%
Similar papers in this journal
- A bHLH interaction code controls bipotential differentiation and self-renewal in the Drosophila gut 96%
- Oct4 mediated inhibition of Lsd1 activity promotes the active and primed state of pluripotency enhancers 95%
- Cell cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.