Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif

Diogo S Castro; Dorota Skowronska-Krawczyk; Olivier Armant; Ian J Donaldson; Carlos Parras; Charles Hunt; James A Critchley; Laurent Nguyen; Achim Gossler; Berthold Göttgens; Jean-Marc Matter; François Guillemot

doi:10.1016/j.devcel.2006.10.006

Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif

Dev Cell. 2006 Dec;11(6):831-44. doi: 10.1016/j.devcel.2006.10.006.

Authors

Diogo S Castro¹, Dorota Skowronska-Krawczyk, Olivier Armant, Ian J Donaldson, Carlos Parras, Charles Hunt, James A Critchley, Laurent Nguyen, Achim Gossler, Berthold Göttgens, Jean-Marc Matter, François Guillemot

Affiliation

¹ Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.

PMID: 17141158
DOI: 10.1016/j.devcel.2006.10.006

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Base Sequence
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Cell Differentiation
Cell Movement
Chick Embryo
Chromatin Immunoprecipitation
DNA / metabolism*
Electroporation
Gene Expression Regulation, Developmental
Intracellular Signaling Peptides and Proteins
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Mice
Mice, Transgenic
Molecular Sequence Data
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neurons / cytology*
Neurons / metabolism
POU Domain Factors / genetics
POU Domain Factors / metabolism*
Promoter Regions, Genetic
Regulatory Sequences, Nucleic Acid / physiology*
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Stem Cells / metabolism
Transcription, Genetic
Transfection

Substances

Ascl1 protein, mouse
Basic Helix-Loop-Helix Transcription Factors
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Nerve Tissue Proteins
POU Domain Factors
delta protein
Pou3f3 protein, mouse
Pou3f2 protein, mouse
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding