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RLS-associated MEIS transcription factors control distinct processes in human neural stem cells
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RLS-associated MEIS transcription factors control distinct processes in human neural stem cells
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Journal Article
RLS-associated MEIS transcription factors control distinct processes in human neural stem cells
2024
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Biochemistry, Molecular Biology
/ CRISPR
/ Genomics
/ Homeobox
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Myeloid Ecotropic Viral Integration Site 1 Protein - genetics
/ Myeloid Ecotropic Viral Integration Site 1 Protein - metabolism
/ Neural Stem Cells - cytology
/ Neural Stem Cells - metabolism
/ Proteins
/ Restless Legs Syndrome - genetics
/ Restless Legs Syndrome - metabolism
/ Science
/ Transcription Factors - genetics
