proteins undergo ubiquitination and are then degraded. This derepresses the auxin response factors so they may carry out their functions in the cell. Altered derepression causing diseases Familial Alzheimer’s disease Alzheimer’s is a neurodegenerative disease involving progressive memory loss and other declines in brain function. One common cause of familial Alzheimer’s is mutation in the PSEN1 gene. This gene encodes a protein that cleaves certain intracellular peptides which, once free in the cytoplasm, promote CBPdegradation. Mutations in PSEN1 decrease its production or ability to cleave proteins. This derepresses the CBP proteins, and allows them to perform their function of upregulating transcription of their target genes. Rett syndrome Rett syndrome is a neurodevelopmental disorder involving deterioration of learned language and motor skills, autism, and seizures starting in infancy. Many cases of Rett syndrome are associated with mutations in MECP2, a gene encoding a transcriptional repressor. Mutations in this gene decrease the levels of MeCP2 binding to different promoter sequences, resulting in their overall derepression. The increased expression of these MeCP2 regulated genes in neurons contribute to the Rett syndrome phenotype. Beckwith-Wiedemann syndrome This syndrome is associated with increased susceptibility to tumors and growth abnormalities in children. A common cause of this syndrome is a mutation in an imprint control region near the Igf2 gene. This imprint control region is normally bound by an insulator on the maternal allele, which represses an enhancer from acting on the Igf2 gene. This insulator is absent on the paternal allele and allows it access to the gene. Mutations in this imprint control region inhibit the insulator from binding, which derepresses enhancer activity on the maternal Igf2 gene. This abnormal derepression and increase in gene expression can result in Beckwith-Wiedemann syndrome. References Gene expression Genetics techniques Molecular genetics Molecular biology