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The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation

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Item Type:Article
Title:The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation
Creators Name:Benedum, J. and Franke, V. and Appel, L.M. and Walch, L. and Bruno, M. and Schneeweiss, R. and Gruber, J. and Oberndorfer, H. and Frank, E. and Strobl, X. and Polyansky, A. and Zagrovic, B. and Akalin, A. and Slade, D.
Abstract:Transcription is regulated by a multitude of activators and repressors, which bind to the RNA polymerase II (Pol II) machinery and modulate its progression. Death-inducer obliterator 3 (DIDO3) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here, we show that DIDO3 and PHF3 form a complex that bridges the Pol II elongation machinery with chromatin and RNA processing factors and tethers Pol II in a phase-separated microenvironment. Their SPOC domains and C-terminal intrinsically disordered regions are critical for transcription regulation. PHF3 and DIDO exert cooperative and antagonistic effects on the expression of neuronal genes and are both essential for neuronal differentiation. In the absence of PHF3, DIDO3 is upregulated as a compensatory mechanism. In addition to shared gene targets, DIDO specifically regulates genes required for lipid metabolism. Collectively, our work reveals multiple layers of gene expression regulation by the DIDO3 and PHF3 paralogues, which have specific, co-regulatory and redundant functions in transcription.
Keywords:Gene Expression, Neural Stem Cells, Protein-Protein Interaction Networks, Transcription
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:7912
Date:30 November 2023
Official Publication:https://doi.org/10.1038/s41467-023-43724-y
PubMed:View item in PubMed

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