Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif.
Proneural proteins play a central role in vertebrate neurogenesis, but little is known of the genes that they regulate and of the factors that interact with proneural proteins to activate a neurogenic program. Here, we demonstrate that the proneural protein Mash1 and the POU proteins Brn1 and Brn2 interact on the promoter of the Notch ligand Delta1 and synergistically activate Delta1 transcription, a key step in neurogenesis. Overexpression experiments in vivo indicate that Brn2, like Mash1, regulates additional aspects of neurogenesis, including the division of progenitors and the differentiation and migration of neurons. We identify by in silico screening a number of additional candidate target genes, which are recognized by Mash1 and Brn proteins through a DNA-binding motif similar to that found in the Delta1 gene and present a broad range of activities. We thus propose that Mash1 synergizes with Brn factors to regulate multiple steps of neurogenesis.
Castro
Diogo S
DS
Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Skowronska-Krawczyk
Dorota
D
Armant
Olivier
O
Donaldson
Ian J
IJ
Parras
Carlos
C
Hunt
Charles
C
Critchley
James A
JA
Nguyen
Laurent
L
Gossler
Achim
A
Göttgens
Berthold
B
Matter
Jean-Marc
JM
Guillemot
François
F
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism*; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C499317:Ascl1 protein, mouse; C064045:delta protein; C074065:Pou3f3 protein, mouse; C074066:Pou3f2 protein, mouse