An Evolutionarily Conserved SoxB-Hdac2 Crosstalk Regulates Neurogenesis in a Cnidarian.
SoxB transcription factors and histone deacetylases (HDACs) are each major players in the regulation of neurogenesis, but a functional link between them has not been previously demonstrated. Here, we show that SoxB2 and Hdac2 act together to regulate neurogenesis in the cnidarian Hydractinia echinata during tissue homeostasis and head regeneration. We find that misexpression of SoxB genes modifies the number of neural cells in all life stages and interferes with head regeneration. Hdac2 was co-expressed with SoxB2, and its downregulation phenocopied SoxB2 knockdown. We also show that SoxB2 and Hdac2 promote each other's transcript levels, but Hdac2 counteracts this amplification cycle by deacetylating and destabilizing SoxB2 protein. Finally, we present evidence for conservation of these interactions in human neural progenitors. We hypothesize that crosstalk between SoxB transcription factors and Hdac2 is an ancient feature of metazoan neurogenesis and functions to stabilize the correct levels of these multifunctional proteins.
Centre for Chromosome Biology (CCB), School of Natural Sciences, National University of Ireland, Galway H91 CF50, Ireland.
Hakima
H
Flici
Whitney Laboratory for Marine Bioscience, University of Florida, St. Augustine, FL 32080, USA; Department of Biology, University of Florida, Gainesville, FL 32611, USA; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-8002, USA.
Christine E
CE
Schnitzler
Centre for Chromosome Biology (CCB), School of Natural Sciences, National University of Ireland, Galway H91 CF50, Ireland.
R Cathriona
RC
Millane
Centre for Chromosome Biology (CCB), School of Natural Sciences, National University of Ireland, Galway H91 CF50, Ireland.
Graham
G
Govinden
Centre for Chromosome Biology (CCB), School of Natural Sciences, National University of Ireland, Galway H91 CF50, Ireland.
Amy
A
Houlihan
Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Galway H91 CF50, Ireland.
Stephanie D
SD
Boomkamp
Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Galway H91 CF50, Ireland.
Sanbing
S
Shen
Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-8002, USA.
Andreas D
AD
Baxevanis
Centre for Chromosome Biology (CCB), School of Natural Sciences, National University of Ireland, Galway H91 CF50, Ireland. Electronic address: uri.frank@nuigalway.ie.
Uri
U
Frank
D000818:Animals; D005075:Biological Evolution; D003063:Cnidaria / Q000378:metabolism* / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D012038:Regeneration / Q000502:physiology; D055749:SOXB2 Transcription Factors / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology
D055749:SOXB2 Transcription Factors; D056464:Histone Deacetylase 2
Hdac2; Hydractinia; SoxB; cnidaria; evolution; histone deacetylase; nervous system; neurogenesis; regeneration; transcription factor