Retrograde BMP signaling activates neuronal gene expression through widespread deployment of a conserved BMP-responsive cis-regulatory activation element.
Animals
Antigens, Ly
/ genetics
Bone Morphogenetic Proteins
/ physiology
Chick Embryo
DNA-Binding Proteins
/ metabolism
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ genetics
Evolution, Molecular
GPI-Linked Proteins
/ genetics
Neurons
/ metabolism
Response Elements
Signal Transduction
Smad Proteins
/ metabolism
Smad4 Protein
/ metabolism
Transcription Factors
/ metabolism
Transcriptional Activation
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
25 01 2019
25 01 2019
Historique:
received:
19
02
2018
accepted:
25
10
2018
pubmed:
27
11
2018
medline:
21
8
2019
entrez:
27
11
2018
Statut:
ppublish
Résumé
Retrograde Bone Morphogenetic Protein (BMP) signaling in neurons is essential for the differentiation and synaptic function of many neuronal subtypes. BMP signaling regulates these processes via Smad transcription factor activity, yet the scope and nature of Smad-dependent gene regulation in neurons are mostly unknown. Here, we applied a computational approach to predict Smad-binding cis-regulatory BMP-Activating Elements (BMP-AEs) in Drosophila, followed by transgenic in vivo reporter analysis to test their neuronal subtype enhancer activity in the larval central nervous system (CNS). We identified 34 BMP-AE-containing genomic fragments that are responsive to BMP signaling in neurons, and showed that the embedded BMP-AEs are required for this activity. RNA-seq analysis identified BMP-responsive genes in the CNS and revealed that BMP-AEs selectively enrich near BMP-activated genes. These data suggest that functional BMP-AEs control nearby BMP-activated genes, which we validated experimentally. Finally, we demonstrated that the BMP-AE motif mediates a conserved Smad-responsive function in the Drosophila and vertebrate CNS. Our results provide evidence that BMP signaling controls neuronal function by directly coordinating the expression of a battery of genes through widespread deployment of a conserved Smad-responsive cis-regulatory motif.
Identifiants
pubmed: 30476189
pii: 5198513
doi: 10.1093/nar/gky1135
pmc: PMC6344883
doi:
Substances chimiques
Antigens, Ly
0
Bone Morphogenetic Proteins
0
DNA-Binding Proteins
0
Drosophila Proteins
0
GPI-Linked Proteins
0
MAD protein, Drosophila
0
Med protein, Drosophila
0
Smad Proteins
0
Smad4 Protein
0
Transcription Factors
0
twit protein, Drosophila
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
679-699Subventions
Organisme : CIHR
ID : MOP-98011
Pays : Canada
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