The SUMO Pathway Promotes Basic Helix-Loop-Helix Proneural Factor Activity via a Direct Effect on the Zn Finger Protein Senseless

Powell, Lynn M.; Chen, Angela; Huang, Yuxuan; Wang, Pin Yao; Kemp, Sadie; Jarman, Andrew P.

doi:10.1128/mcb.06595-11

Cited by 13 publications

(14 citation statements)

References 71 publications

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“…Most importantly, E(spl) proteins also interact with a StUbl (SUMO-targeted ubiquitin ligase), called Degringolade, and their ubiquitylation seems to decrease their affinity for Gro Barry et al, 2011;Powell et al, 2012). Thanks to their duplication, Drosophila E(spl) can form many homo-and heterodimers with differential affinities for Da, Sc, Ato, and probably other proneural proteins; these preferences are partly mediated by their Orange domains.…”

Section: Closing Remarksmentioning

confidence: 99%

E(spl)

Delidakis

Monastirioti

Magadi

2014

Current Topics in Developmental Biology

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Section: Closing Remarksmentioning

confidence: 99%

E(spl)

Delidakis

Monastirioti

Magadi

2014

Current Topics in Developmental Biology

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“…2). Sens directly binds to proneural proteins, including Atonal, via its Zn-finger domains (24,(64)(65)(66). This interaction enhances the activity of the bHLH factor at its target genes.…”

Section: How Might Atoh1 and Gfi1 Interact?mentioning

confidence: 99%

Atoh1 in sensory hair cell development: constraints and cofactors

Costa

Powell

Lowell

et al. 2017

Seminars in Cell & Developmental Biology

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The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum. The reasons for this context dependence are poorly understood. So far, the pathways and key players that instruct Atoh1 to act as a mechanosensory cell fate determinant in the context of the inner ear are largely unknown. Here we review evidence that suggests that Atoh1 function in hair cell differentiation is modulated by interaction with other transcription factors. We particularly focus on the possible roles of Gfi1 and Pou4f3, drawing from studies in mouse, Drosophila and C. elegans.3

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“…Gfi1 protein contains a SNAG domain which recruits co-repressors (Velinder et al 2016;Zweidler-Mckay et al 1996;Grimes et al 1996), and it acts as a major transcriptional repressor during haematopoiesis (Möröy et al 2015;Möröy and Khandanpour 2011;van der Meer et al 2010). However, the Drosophila orthologue of Gfi1 (Senseless, SENS) (Nolo et al 2000) has been reported to have dual functionality: SENS can act as a DNA-binding transcriptional repressor but also as a transcriptional co-activator of proneural TFs (including Atonal), enhancing their ability to stimulate sensory gene expression (Acar et al 2006;Jafar-Nejad et al 2003a;Powell et al 2008;2012b). Our observation of two distinct populations of Gfi1 sites in iHCs suggests that Gfi1 may similarly have dual functionality.…”

Section: Gfi1 Regulates Hc Differentiation Through Both Repression Anmentioning

confidence: 81%

Atoh1 is repurposed from neuronal to hair cell determinant by Gfi1 acting as a coactivator without redistribution of its genomic binding sites

Costa

Powell

Soufi

et al. 2019

Preprint

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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 Atoh1's 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.

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The SUMO Pathway Promotes Basic Helix-Loop-Helix Proneural Factor Activity via a Direct Effect on the Zn Finger Protein Senseless

Cited by 13 publications

References 71 publications

E(spl)

E(spl)

Atoh1 in sensory hair cell development: constraints and cofactors

Atoh1 is repurposed from neuronal to hair cell determinant by Gfi1 acting as a coactivator without redistribution of its genomic binding sites

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