Histone acetylation deficits in lymphoblastoid cell lines from patients with rubinstein-Taybi syndrome

J. P. Lopez-Atalaya, C. Gervasini, F. Mottadelli, S. Spena, M. Piccione, G. Scarano, A. Selicorni, A. Barco, L. Larizza

Research output: Contribution to journalArticlepeer-review


Background: Rubinstein-Taybi syndrome (RSTS) is a congenital neurodevelopmental disorder defined by postnatal growth deficiency, characteristic skeletal abnormalities and mental retardation and caused by mutations in the genes encoding for the transcriptional co-activators with intrinsic lysine acetyltransferase (KAT) activity CBP and p300. Previous studies have shown that neuronal histone acetylation is reduced in mouse models of RSTS. Methods: The authors identified different mutations at the CREBBP locus and generated lymphoblastoid cell lines derived from nine patients with RSTS carrying distinct CREBBP mutations that illustrate different grades of the clinical severity in the spectrum of the syndrome. They next assessed whether histone acetylation levels were altered in these cell lines. Results: The comparison of CREBBP-mutated RSTS cell lines with cell lines derived from patients with an unrelated mental retardation syndrome or healthy controls revealed significant deficits in histone acetylation, affecting primarily histone H2B and histone H2A. The most severe defects were observed in the lines carrying the whole deletion of the CREBBP gene and the truncating mutation, both leading to a haploinsufficiency state. Interestingly, this deficit was rescued by treatment with an inhibitor of histone deacetylases (HDACi). Conclusions: The authors' results extend to humans the seminal observations in RSTS mouse models and point to histone acetylation defects, mainly involving H2B and H2A, as relevant molecular markers of the disease.

Original languageEnglish
Pages (from-to)66-74
Number of pages9
JournalJournal of Medical Genetics
Issue number1
Publication statusPublished - Jan 2012

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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