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RLS-associated MEIS transcription factors control distinct processes in human neural stem cells.
Sci. Rep. 14:28986 (2024)
MEIS1 and MEIS2 encode highly conserved homeodomain transcription factors crucial for developmental processes in a wide range of tissues, including the brain. They can execute redundant functions when co-expressed in the same cell types, but their roles during early stages of neural differentiation have not been systematically compared. By separate knockout and overexpression of MEIS1 and MEIS2 in human neural stem cells, we find they control specific sets of target genes, associated with distinct biological processes. Integration of DNA binding sites with differential transcriptomics implicates MEIS1 to co-regulate gene expression by interaction with transcription factors of the SOX and FOX families. MEIS1 harbors the strongest risk factor for restless legs syndrome (RLS). Our data suggest that MEIS1 can directly regulate the RLS-associated genes NTNG1, MDGA1 and DACH1, constituting new approaches to study the elusive pathomechanism or RLS.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Restless Legs Syndrome; Genome-wide Association; Lateral Ganglionic Eminence; Dna-binding Partners; Medium Spiny Neurons; Homeobox Genes; Pbx; Expression; Proteins; Prep1
ISSN (print) / ISBN
2045-2322
e-ISSN
2045-2322
Journal
Scientific Reports
Quellenangaben
Volume: 14,
Issue: 1,
Article Number: 28986
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Neurogenomics (ING)
Grants
Helmholtz Zentrum Munchen - Deutsches Forschungszentrum fur Gesundheit und Umwelt (GmbH)
Projekt DEAL
Projekt DEAL