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Evidence for a Nuclear Role for Drosophila Dlg as a Regulator of the NURF Complex

ABSTRACT: Scrib, Dlg, and Lgl are basolateral regulators of epithelial polarity and tumor suppressors whose molecular mechanisms of action remain unclear. We used proximity biotinylation to identify proteins localized near Dlg in the Drosophila wing imaginal disc epithelium. In addition to expected membrane- and cytoskeleton-associated protein classes, nuclear proteins were prevalent in the resulting mass spectrometry data set, including all four members of the NURF chromatin remodeling complex. Subcellular fractionation demonstrated a nuclear pool of Dlg and proximity ligation confirmed its position near the NURF complex. Genetic analysis showed that NURF activity is also required for the overgrowth of dlg tumors, and this growth suppression correlated with a reduction in Hippo pathway gene expression. Together, these data suggest a nuclear role for Dlg in regulating chromatin and transcription through a more direct mechanism than previously thought.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Drosophila Melanogaster (ncbitaxon:7227)

SUBMITTER: David Bilder

PROVIDER: MSV000087186 | MassIVE | Tue Apr 13 17:06:00 BST 2021

SECONDARY ACCESSION(S): PXD025378

REPOSITORIES: MassIVE

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Evidence for a nuclear role for <i>Drosophila</i> Dlg as a regulator of the NURF complex.

Sharp Katherine A KA Khoury Mark J MJ Wirtz-Peitz Frederick F Bilder David D

Molecular biology of the cell 20210908 21

Scribble (Scrib), Discs-large (Dlg), and Lethal giant larvae (Lgl) are basolateral regulators of epithelial polarity and tumor suppressors whose molecular mechanisms of action remain unclear. We used proximity biotinylation to identify proteins localized near Dlg in the <i>Drosophila</i> wing imaginal disc epithelium. In addition to expected membrane- and cytoskeleton-associated protein classes, nuclear proteins were prevalent in the resulting mass spectrometry dataset, including all four member ...[more]

PMID: 34495684

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Project description:This SuperSeries is composed of the following subset Series: GSE10697: Self-Self Hybridisation were used to set confidence 99% intervals GSE10698: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 1 GSE10699: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 2 Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. Keywords: SuperSeries Refer to individual Series

Dataset Information

Evidence for a Nuclear Role for Drosophila Dlg as a Regulator of the NURF Complex

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Publications

Evidence for a nuclear role for <i>Drosophila</i> Dlg as a regulator of the NURF complex.

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Dataset Information

Evidence for a Nuclear Role for Drosophila Dlg as a Regulator of the NURF Complex

Dataset's files

Publications

Evidence for a nuclear role for &lt;i&gt;Drosophila&lt;/i&gt; Dlg as a regulator of the NURF complex.

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OmicsDI is part of the ELIXIR infrastructure

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Evidence for a nuclear role for <i>Drosophila</i> Dlg as a regulator of the NURF complex.