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KAT3 proteins are dispensable for proliferation of neural progenitors but essential fur neural differentiation

AuthorsGonzález-Martínez, Rocio; Blanco, Beatriz del; Barco, Ángel ; Herrera, Eloisa CSIC ORCID
Issue Date2019
CitationEuropean Developmental Biology Congress (2019)
AbstractRubinstein-Taybi syndrome (RSTS) is a genetic neurodevelopmental disorder characterized by mental impairment and a wide spectrum of congenital abnormalities, that is caused by hemizygous mutations in the genes encoding the KAT3 family of transcriptional coactivator CREB binding protein (CBP) and the E1A binding protein P300 (p300). Both factors have intrinsic lysine acetyltransferase (KAT) activity and are critically involved in the transcriptional and epigenetic regulation of gene expression. Consistent with this central role, both CBP and p300 knockout (KO) mice exhibit early embryonic death and neuronal tube closure defects. However, the precise function of these proteins during the development of the central nervous system has not been clearly stated. Here we assess whether KAT3 proteins are necessary for proliferation and neuronal differentiation that could explain some of the neurological alterations associated with RSTS. Experiments performed with neurospheres demonstrate that cell proliferation is normal in the absence of CBP or P300 but it is affected in the absence of both acetyltransferases. However, neuronal differentiation is seriously compromised in neurospheres lacking any of the two proteins. In vivo, CBP deletion in progenitors have a negative impact in the number of differentiated retinal neutrons in contrast to the lack of P300 that has not an impact in the number of neurons. CBP and P300 deletion in differentiated retinal neurons (using Brn3b-Cre line) demonstrate that CBP and P300 are not essential for neuronal viability or identity but these processes are affected when both proteins are eliminated. Ongoing sequencing experiments should further clarify the role of KAT3 proteins in neural differentiation and reveal the redundancy between these two paralog transcriptional coactivators.
DescriptionResumen del póster presentado al European Developmental Biology Congress (EDBC), celebrado en Alicante del 23 al 26 de octubre de 2019.
Appears in Collections:(IN) Comunicaciones congresos
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