RESUMO
One X chromosome, selected at random, is silenced in each female mammalian cell. Xist encodes a noncoding RNA that influences the probability that the cis-linked X chromosome will be silenced. We found that the A-repeat, a highly conserved element within Xist, is required for the accumulation of spliced Xist RNA. In addition, the A-repeat is necessary for X-inactivation to occur randomly. In combination, our data suggest that normal Xist RNA processing is important in the regulation of random X-inactivation. We propose that modulation of Xist RNA processing may be part of the stochastic process that determines which X chromosome will be inactivated.
Assuntos
Proteínas Nucleares/metabolismo , Processamento Pós-Transcricional do RNA , RNA não Traduzido/genética , Proteínas de Ligação a RNA/metabolismo , Sequências Repetitivas de Ácido Nucleico/genética , Inativação do Cromossomo X/genética , Alelos , Animais , Sequência de Bases , Cromossomos de Mamíferos/metabolismo , Feminino , Células HeLa , Histonas/metabolismo , Humanos , Masculino , Camundongos , Modelos Biológicos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Ligação Proteica , Processamento de Proteína Pós-Traducional , RNA Longo não Codificante , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA não Traduzido/química , Deleção de Sequência/genética , Fatores de Processamento de Serina-ArgininaRESUMO
In female mammals, one X chromosome is transcriptionally silenced to achieve dosage compensation between XX females and XY males. This process, known as X-inactivation, occurs early in development, such that one X chromosome is silenced in every cell. Once X-inactivation has occurred, the inactive X chromosome is marked by a unique set of epigenetic features that distinguishes it from the active X chromosome and autosomes. These modifications appear sequentially during the transition from a transcriptionally active to an inactive state and, once established, act redundantly to maintain transcriptional silencing. In this review, we survey the unique epigenetic features that characterize the inactive X chromosome, describe the mechanisms by which these marks are established and maintained, and discuss how each contributes to silencing the inactive X chromosome.
