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Rubinstein-Taybi Syndrome and Epigenetic Alterations.
- Source :
-
Advances in experimental medicine and biology [Adv Exp Med Biol] 2017; Vol. 978, pp. 39-62. - Publication Year :
- 2017
-
Abstract
- Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue. Recent studies of the epigenetic mechanisms underlying cognitive functions in mice provide direct evidence for the involvement of nuclear factors (e.g., CBP) in the control of higher cognitive functions. In fact, a role for CBP in higher cognitive function is suggested by the finding that RSTS is caused by heterozygous mutations at the CBP locus (Petrij et al., Nature 376:348-351, 1995). CBP was demonstrated to possess an intrinsic histone acetyltransferase activity (Ogryzko et al., Cell 87:953-959, 1996) that is required for CREB-mediated gene expression (Korzus et al., Science 279:703-707, 1998). The intrinsic protein acetyltransferase activity in CBP might directly destabilize promoter-bound nucleosomes, facilitating the activation of transcription. Due to the complexity of developmental abnormalities and the possible genetic compensation associated with this congenital disorder, however, it is difficult to establish a direct role for CBP in cognitive function in the adult brain. Although aspects of the clinical presentation in RSTS cases have been extensively studied, a spectrum of symptoms found in RSTS patients can be accessed only after birth, and, thus, prenatal genetic tests for this extremely rare genetic disorder are seldom considered. Even though there has been intensive research on the genetic and epigenetic function of the CREBBP gene in rodents, the etiology of this devastating congenital human disorder is largely unknown.
- Subjects :
- Acetylation
Animals
Brain metabolism
Brain pathology
CREB-Binding Protein deficiency
CREB-Binding Protein genetics
Cognition physiology
Disease Models, Animal
E1A-Associated p300 Protein deficiency
E1A-Associated p300 Protein genetics
Gene Expression Regulation, Developmental
Genetic Association Studies
Histone Acetyltransferases deficiency
Histone Acetyltransferases genetics
Histone Code genetics
Histone Deacetylase Inhibitors therapeutic use
Humans
Invertebrates genetics
Invertebrates physiology
Mammals genetics
Mammals physiology
Memory physiology
Models, Neurological
Mutation
Nerve Tissue Proteins deficiency
Nerve Tissue Proteins genetics
RNA, Long Noncoding genetics
Rubinstein-Taybi Syndrome metabolism
CREB-Binding Protein physiology
E1A-Associated p300 Protein physiology
Epigenesis, Genetic genetics
Histone Acetyltransferases physiology
Histone Code physiology
Nerve Tissue Proteins physiology
Protein Processing, Post-Translational genetics
Rubinstein-Taybi Syndrome genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0065-2598
- Volume :
- 978
- Database :
- MEDLINE
- Journal :
- Advances in experimental medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 28523540
- Full Text :
- https://doi.org/10.1007/978-3-319-53889-1_3