Genome-Wide RNAi Screen Identify Melanoma-Associated Antigen Mageb3 Involved in X Chromosome Inactivation.
Xist (inactivated X chromosome specific transcript) is a prototype long noncoding RNA in charge of epigenetic silencing of one X chromosome in each female cell in mammals. In a genetic screen, we identify Mageb3 and its homologs Mageb1 and Mageb2 as genes functionally required for Xist-mediated gene silencing. Mageb1-3 are previously uncharacterized genes belonging to the MAGE (melanoma-associated antigen) gene family. Mageb1-3 are expressed in undifferentiated ES cells and early stages of in vitro differentiation, a critical time window of X chromosome inactivation. Mageb3 showed both cytoplasmic and nuclear localization without enrichment on the inactive X (Xi). Mageb3 interacted with Polycomb group ring finger 3 (Pcgf3), a RING finger protein involved in recruiting Polycomb activities onto Xi. Mageb3 overexpression stabilized Pcgf3 protein. Mageb1-3 gene knockout affected H3K27me3 enrichment and the spreading of gene silencing along Xi. These data suggested that Mageb3 might regulate the recruitment of the Polycomb complex onto Xi and subsequent H3K27me3 modification through Pcgf3. Moreover, the nucleolar enrichment of Mageb3 was diminished when nuclear matrix factor hnRNP U is overexpressed, implying the interaction between Mageb3 and nuclear matrix, which is another possible mechanism for Mageb3 to regulate X chromosome inactivation.
['Li|Wei|W|', 'Hong|Ru|R|', 'Lai|Lan-Tian|LT|', 'Dong|Qiman|Q|', 'Ni|Peiling|P|', 'Chelliah|Rosi|R|', 'Huq|Mehnaz|M|', 'Ismail|Siti Nadirah Binte|SNB|', 'Chandola|Udita|U|', 'Ang|Zhiwei|Z|', 'Lin|Bingqing|B|', 'Chen|Xin|X|', 'Chen|Lingyi|L|', 'Zhang|Li-Feng|LF|']
D000818:Animals D000951:Antigens, Neoplasm D002467:Cell Nucleus D004622:Embryo, Mammalian D005347:Fibroblasts D020868:Gene Silencing D016678:Genome D034722:Heterogeneous-Nuclear Ribonucleoprotein U D008297:Male D051379:Mice D009363:Neoplasm Proteins D063146:Polycomb-Group Proteins D034622:RNA Interference D013347:Subcellular Fractions D014158:Transcription, Genetic D049951:X Chromosome Inactivation
Mageb3 Xist nuclear matrix hnRNP U chromatin architecture