Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Cell. 2016 Jan 28;164(3):460-75. doi: 10.1016/j.cell.2015.12.048.

Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis.

Author information

1
VIB Center for the Biology of Disease, VIB, 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium.
2
VIB Center for the Biology of Disease, VIB, 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Program in Molecular and Developmental Genetics, Doctoral School for Biomedical Sciences, University of Leuven School Group Biomedicine, 3000 Leuven, Belgium.
3
Welbio, Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 1070 Brussels, Belgium.
4
VIB Switch Laboratory, 3000 Leuven, Belgium; Department for Cellular and Molecular Medicine, University of Leuven School of Medicine, 3000 Leuven, Belgium.
5
Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
6
Laboratory of Biosignaling and Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven School of Medicine, 3000 Leuven, Belgium.
7
Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
8
VIB Center for the Biology of Disease, VIB, 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Welbio, Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 1070 Brussels, Belgium.
9
VIB Center for the Biology of Disease, VIB, 3000 Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, 3000 Leuven, Belgium; Program in Molecular and Developmental Genetics, Doctoral School for Biomedical Sciences, University of Leuven School Group Biomedicine, 3000 Leuven, Belgium. Electronic address: bassem.hassan@icm-institute.org.

Abstract

Neurogenesis is initiated by the transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators. Here, we discover a conserved post-translational switch governing the duration of proneural protein activity that is required for proper neuronal development. Phosphorylation of a single Serine at the same position in Scute and Atonal proneural proteins governs the transition from active to inactive forms by regulating DNA binding. The equivalent Neurogenin2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex. Using genome editing in Drosophila, we show that Atonal outlives its mRNA but is inactivated by phosphorylation. Inhibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expression dynamics and target gene expression resulting in neuronal number and fate defects. Strikingly, even a subtle change from Serine to Threonine appears to shift the duration of Atonal activity in vivo, resulting in neuronal fate defects.

Comment in

PMID:
26824657
DOI:
10.1016/j.cell.2015.12.048
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center