A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced.

By Julie Chaumeil, Patricia Le Baccon, Anton Wutz, Edith Heard. 2006

519 citations recorded by the source corpus.

During early mammalian female development, one of the two X chromosomes becomes inactivated. Although X-chromosome coating by Xist RNA is essential for the initiation of X inactivation, little is known about how this signal is transformed into transcriptional silencing. Here we show that exclusion of RNA Polymerase II and transcription factors from the Xist RNA-coated X chromosome represents the earliest event following Xist RNA accumulation described so far in differentiating embryonic stem (ES) cells. Paradoxically, exclusion of the transcription machinery occurs before gene silencing is complete. However, examination of the three-dimensional organization of X-linked genes reveals that, when transcribed, they are always located at the periphery of, or outside, the Xist RNA domain, in contact with the transcription machinery. Upon silencing, genes shift to a more internal location, within the Xist RNA compartment devoid of transcription factors. Surprisingly, the appearance of this compartment is not dependent on the A-repeats of the Xist transcript, which are essential for gene silencing. However, the A-repeats are required for the relocation of genes into the Xist RNA silent domain. We propose that Xist RNA has multiple functions: A-repeat-independent creation of a transcriptionally silent nuclear compartment; and A-repeat-dependent induction of gene repression, which is associated with their translocation into this silent domain.

Subfields: Genetics, Molecular Biology

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Citations in the corpus

The H19 Non-Coding RNA Is Essential for Human Tumor Growth (2007, background): “X–inactivation is controlled by the non–coding RNA transcript Xist through an epigenetic mechanism [13].”
No-nonsense functions for long noncoding RNAs. (2011, background): “They focused on RNAPII-binding peaks and noncoding transcription outside of protein-coding genes during macrophage activation and matched these extragenic sites with distinct chromatin signatures characteristic of enhancers.”
Molecular Interplay of the Non-coding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a (2010, unknown): “…et al., 2007), believed to control gene silencing by recruiting histone methyltransferases, such as by Air (Nagano et al., 2008) and Kcnq1ot1 (Pandey et al., 2008), or by creating a repressed nuclear compartment to which target genes are relocated, such as by Xist (Chaumeil et al., 2006).”
Stability and flexibility of epigenetic gene regulation in mammalian development (2007, background): “This might establish a physical structure from which RNA polymerase II (Pol II) is excluded, resulting in transcriptional silencin”
A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA (2011, unknown): “…in mediating epigenetic changes through recruitment of the Polycomb Repressive Complex (PRC) was described for the Xist and HOTAIR transcripts (Chaumeil et al., 2006; Rinn et al., 2007). lncRNAs were also found to act in the nucleus as antisense transcripts or as decoy for splicing factors…”
Nuclear organization of the genome and the potential for gene regulation (2007, background): “The first event that occurs after Xist RNA coats the chromosome to be inactivated is that Pol II is excluded from the compartment that contains the bulk of the X-chromosome territor”
Xist nucleates local protein gradients to propagate silencing across the X chromosome (2021, background): “6176 Cell 184, 6174–6192, December 9, 2021 silencing are stepwise processes (Chaumeil et al., 2006) and establish the D2 to D4 transition as a critical window for dissecting the relationship between Xist, its interacting proteins, and gradual gene silencing.”
Child health, developmental plasticity, and epigenetic programming. (2011, background): “Another lncRNA, X inactive-specific transcript gene (Xist), which is transcribed specifically from the inactive X-chromosome, coats the chromosome in cis to help create a repressive environment with recruitment of histone modifications and DNA methylation (123) (see also Section IV.”
Evolution and functions of long noncoding RNAs. (2009, background): “Indeed, it is now thought that the Xist RNA establishes a specialized nuclear compartment devoid of Pol II, into which most of the chromatin of the future inactive X chromosome becomes localized during inactivation (Chaumeil et al., 2006).”
Systematic discovery of Xist RNA binding proteins (2015, background): “Imaging studies suggested that Xist RNA create a transcriptionally inactive nuclear compartment, independent of the A-repeat, but that the A-repeat is required for the movement of genes into this compartment as they become silenced (Chaumeil et al., 2006).”