Polycomb group complexes are recruited to reactivated FMR1 alleles in Fragile X syndrome in response to FMR1 transcription

• Published in: Human molecular genetics Vol. 23; no. 24; pp. 6575 - 6583
• Main Authors: Kumari, D., Usdin, K.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.12.2014
• Subjects: Alleles; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Cell Line; Enhancer of Zeste Homolog 2 Protein; Enzyme Inhibitors - pharmacology; Fragile X Mental Retardation Protein - antagonists & inhibitors; Fragile X Mental Retardation Protein - genetics; Fragile X Mental Retardation Protein - metabolism; Fragile X Syndrome - genetics; Fragile X Syndrome - metabolism; Fragile X Syndrome - pathology; Gene Expression Regulation; Histones - genetics; Histones - metabolism; Humans; Lymphocytes - drug effects; Lymphocytes - metabolism; Lymphocytes - pathology; Male; Naphthalenes - pharmacology; Polycomb Repressive Complex 2 - genetics; Polycomb Repressive Complex 2 - metabolism; Pyrones - pharmacology; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Sirtuin 1 - antagonists & inhibitors; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Transcription, Genetic

The FMR1 gene is subject to repeat mediated-gene silencing when the CGG-repeat tract in the 5' UTR exceeds 200 repeat units. This results in Fragile X syndrome, the most common heritable cause of intellectual disability and a major cause of autism spectrum disorders. The mechanism of gene silen...