Building up the inactive X chromosome<sup>1</sup>

Matarazzo, Maria R.; Cerase, Andrea; D’Esposito, Maurizio

doi:10.1042/bc20070073

Cited by 5 publications

(6 citation statements)

References 63 publications

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“…This triggers a cascade of events, including the acquisition of repressive chromatin modifications, exclusion of RNA polymerase II (Pol II) and removal of active histone marks, histone exchange and DNA methylation. These events act in concert to ensure the stable repression of the entire chromosome and the maintenance of the silent state (maintenance phase of XCI) [ 2 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

Xist localization and function: new insights from multiple levels

et al. 2015

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In female m ammals, one of the two X chromosomes in each cell is transcriptionally silenced in order to achieve dosage compensation between the genders in a process called X chromosome inactivation. The master regulator of this process is the long non-coding RNA Xist. During X-inactivation, Xist accumulates in cis on the future inactive X chromosome, triggering a cascade of events that provoke the stable silencing of the entire chromosome, with relatively few genes remaining active. How Xist spreads, what are its binding sites, how it recruits silencing factors and how it induces a specific topological and nuclear organization of the chromatin all remain largely unanswered questions. Recent studies have improved our understanding of Xist localization and the proteins with which it interacts, allowing a reappraisal of ideas about Xist function. We discuss recent advances in our knowledge of Xist-mediated silencing, focusing on Xist spreading, the nuclear organization of the inactive X chromosome, recruitment of the polycomb complex and the role of the nuclear matrix in the process of X chromosome inactivation.

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Section: Introductionmentioning

confidence: 99%

Xist localization and function: new insights from multiple levels

et al. 2015

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“…The mechanism by which Xist RNA coats the inactive X chromosome and spreads this signal is unknown, but Xist binding precedes other changes in the chromosome including alteration of the methylation and acetylation states of histones, late replication, and methylation of CpG islands for those genes which undergo X inactivation [11]–[13]. Chromosomal localization studies have now shown that Xist coating of the inactive X chromosome leads to formation of a nuclear compartment which excludes the transcription machinery [14]–[16], yet it remains unclear what molecular components are involved in this process.…”

Section: Introductionmentioning

confidence: 99%

X Chromosome Inactivation and Xist Evolution in a Rodent Lacking LINE-1 Activity

2009

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Dosage compensation in eutherian mammals occurs by inactivation of one X chromosome in females. Silencing of that X chromosome is initiated by Xist, a large non-coding RNA, whose coating of the chromosome extends in cis from the X inactivation center. LINE-1 (L1) retrotransposons have been implicated as possible players for propagation of the Xist signal, but it has remained unclear whether they are essential components. We previously identified a group of South American rodents in which L1 retrotransposition ceased over 8 million years ago and have now determined that at least one species of these rodents, Oryzomys palustris, still retains X inactivation. We have also isolated and analyzed the majority of the Xist RNA from O. palustris and a sister species retaining L1 activity, Sigmodon hispidus, to determine if evolution in these sequences has left signatures that might suggest a critical role for L1 elements in Xist function. Comparison of rates of Xist evolution in the two species fails to support L1 involvement, although other explanations are possible. Similarly, comparison of known repeats and potential RNA secondary structures reveals no major differences with the exception of a new repeat in O. palustris that has potential to form new secondary structures.

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“…In addition to mouse and human LINEs and Xist/XIST RNA, we explored LINEs and Rsx RNA from the marsupial opossum, which uses different XCI mechanisms, such as non-random (or imprinted) XCI, and has a different genome composition, as shown by similar L1 occupancy on the X chromosome and autosomes (Fig. 4a, this study; [14, 23]). Owing to the generally low levels of the sequence conservation of lncRNAs [59] and species-specific LINE elements [60–62], this wider target of species in mammals (both eutherians and metatherians) may help in explaining the common features of interaction motifs required for Xist/XIST/Rsx lncRNA–chromatin associations in XCI.…”

Section: Discussionmentioning

confidence: 99%

“…L1 elements have been identified in all mammalian species, including both metatherians (marsupial mammals) and eutherians (placental mammals). However, the X chromosome of the marsupial opossum, unlike that in eutherians, does not show L1 enrichment compared to autosomes [14, 23], a finding which is, according to the Lyon repeat hypothesis, consistent with the observation of incomplete XCI in marsupials [24, 25]. Thus, it can be considered that, despite the dissimilarity in both the L1 contents in the X chromosome and the Xist/XIST/Rsx RNA sequences, epigenetic features of the XCI process are conserved across metatherians and eutherians [6, 24, 26].…”

Section: Introductionmentioning

confidence: 99%

Convergence in LINE-1 nucleotide variations can benefit redundantly forming triplexes with lncRNA in mammalian X-chromosome inactivation

2019

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Background Associations between X-inactive transcript (Xist)–long noncoding RNA (lncRNA) and chromatin are critical intermolecular interactions in the X-chromosome inactivation (XCI) process. Despite high-resolution analyses of the Xist RNA-binding sites, specific interaction sequences are yet to be identified. Based on elusive features of the association between Xist RNA and chromatin and the possible existence of multiple low-affinity binding sites in Xist RNA, we defined short motifs (≥5 nucleotides), termed as redundant UC/TC (r-UC/TC) or AG (r-AG) motifs, which may help in the mediation of triplex formation between the lncRNAs and duplex DNA. Results The study showed that r-UC motifs are densely dispersed throughout mouse and human Xist/XIST RNAs, whereas r-AG motifs are even more densely dispersed along opossum RNA-on-the-silent X (Rsx) RNA, and also along both full-length and truncated long interspersed nuclear elements (LINE-1s, L1s) of the three species. Predicted secondary structures of the lncRNAs showed that the length range of these sequence motifs available for forming triplexes was even shorter, mainly 5- to 9-nucleotides long. Quartz crystal microbalance (QCM) measurements and Monte Carlo (MC) simulations indicated that minimum-length motifs can reinforce the binding state by increasing the copy number of the motifs in the same RNA or DNA molecule. Further, r-AG motifs in L1s had a similar length-distribution pattern, regardless of the similarities in the length or sequence of L1s across the three species; this also applies to high-frequency mutations in r-AG motifs, which suggests convergence in L1 sequence variations. Conclusions Multiple short motifs in both RNA and duplex DNA molecules could be brought together to form triplexes with either Hoogsteen or reverse Hoogsteen hydrogen bonding, by which their associations are cooperatively enhanced. This novel triplex interaction could be involved in associations between lncRNA and chromatin in XCI, particularly at the sites of L1s. Potential binding of Xist/XIST/Rsx RNAs specifically at L1s is most likely preserved through the r-AG motifs conserved in mammalian L1s through convergence in L1 nucleotide variations and by maintaining a particular r-UC/r-AG motif ratio in each of these lncRNAs, irrespective of their poorly conserved sequences. Electronic supplementary material The online version of this article (10.1186/s13100-019-0173-4) contains supplementary material, which is available to authorized users.

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Building up the inactive X chromosome¹

Cited by 5 publications

References 63 publications

Xist localization and function: new insights from multiple levels

Xist localization and function: new insights from multiple levels

X Chromosome Inactivation and Xist Evolution in a Rodent Lacking LINE-1 Activity

Convergence in LINE-1 nucleotide variations can benefit redundantly forming triplexes with lncRNA in mammalian X-chromosome inactivation

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Building up the inactive X chromosome1

Cited by 5 publications

References 63 publications

Xist localization and function: new insights from multiple levels

Xist localization and function: new insights from multiple levels

X Chromosome Inactivation and Xist Evolution in a Rodent Lacking LINE-1 Activity

Convergence in LINE-1 nucleotide variations can benefit redundantly forming triplexes with lncRNA in mammalian X-chromosome inactivation

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About

Building up the inactive X chromosome¹