Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene. [5] [6] [7]
Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene. [5] [6] [7]
Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. ATRX is required for deposition of the histone variant H3.3 at telomeres and other genomic repeats. [8] These interactions are important for maintaining silencing at these sites. [9] [10] [11]
In addition, ATRX undergoes cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis. [7]
Inherited mutations of the ATRX gene are associated with an X-linked mental retardation (XLMR) syndrome most often accompanied by alpha-thalassemia (ATR-X) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. Female carriers may demonstrate skewed X chromosome inactivation. [7]
Acquired mutations in ATRX have been reported in a number of human cancers including pancreatic neuroendocrine tumours, [12] gliomas, [13] [14] osteosarcomas, [15] soft-tissue sarcomas, [16] and malignant pheochromocytomas. [17] There is a strong correlation between ATRX mutations and an Alternative Lengthening of Telomeres (ALT) [ broken anchor ] phenotype in cancers. [12]
ATRX forms a complex with DAXX which is an histone H3.3 chaperone. [18]