X-Chromosome Kiss and Tell: How the Xs Go Their Separate Ways

Anguera, Montserrat C.; Sun, Bryan K.; Xu, Na; Lee, J.T.

doi:10.1101/sqb.2006.71.012

Cited by 27 publications

(17 citation statements)

References 76 publications

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“…Symmetry break mediated by pairing and Tsix. Adapted from (Anguera et al 2006) and (Lee 2009): In the pre-XCI state, the Xs are epigenetically equivalent, both expressing Tsix at high levels and Xist at low basal levels. Falling levels of Oct4 during cell differentiation triggers X-X pairing.…”

Section: Rna In Pairing Counting and Choicementioning

confidence: 99%

The X as Model for RNA's Niche in Epigenomic Regulation

Lee¹

2010

Cold Spring Harbor Perspectives in Biology

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SUMMARYThe X-linked region now known as the "X-inactivation center" (Xic) was once dominated by protein-coding genes but, with the rise of Eutherian mammals some 150 -200 million years ago, became infiltrated by genes that produce long noncoding RNA (ncRNA). Some of the noncoding genes have been shown to play crucial roles during X-chromosome inactivation (XCI), including the targeting of chromatin modifiers to the X. The rapid establishment of ncRNA hints at a possible preference for long transcripts in some aspects of epigenetic regulation. This article discusses the role of RNA in XCI and considers the advantages RNA offers in delivering allelic, cis-limited, and locus-specific control. Unlike proteins and small RNAs, long ncRNAs are tethered to the site of transcription and effectively tag the allele of origin. Furthermore, long ncRNAs are drawn from larger sequence space than proteins and can mark a unique region in a complex genome. Thus, like their small RNA cousins, long ncRNAs may emerge as versatile and powerful regulators of the epigenome.

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Section: Rna In Pairing Counting and Choicementioning

confidence: 99%

The X as Model for RNA's Niche in Epigenomic Regulation

Lee¹

2010

Cold Spring Harbor Perspectives in Biology

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“…The subsequent discovery of the transient pairing of Xs in ES cells led to the realization that physical association provides a unique opportunity for the Xs to communicate directly (Anguera et al 2006;Bacher et al 2006;Carrel 2006;Xu et al 2006). By fluorescence in situ hybridization (FISH), it was observed that, at the onset of cell differentiation and just prior to the initiation of chromosome-wide silencing, the Xs briefly make contact at the Xic.…”

Section: X-chromosome Pairing Controlled By Transcription Of Ncrnamentioning

confidence: 99%

“…It therefore has been proposed that protein and RNA may collaborate to bring the Xs together and facilitate the Anguera et al (2006). The two X chromosomes are epigenetically identical and euchromatic in the pre-XCI stage.…”

Section: X-chromosome Pairing Controlled By Transcription Of Ncrnamentioning

confidence: 99%

Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome

Lee¹

2009

Genes Dev.

328

266

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Transcriptome studies are revealing that the eukaryotic genome actively transcribes a diverse repertoire of large noncoding RNAs (ncRNAs), many of which are unannotated and distinct from the small RNAs that have garnered much attention in recent years. Why are they so pervasive, and do they have a function? X-chromosome inactivation (XCI) is a classic epigenetic phenomenon associated with many large ncRNAs. Here, I provide a perspective on how XCI is achieved in mice and suggest how this knowledge can be applied to the rest of the genome. Emerging data indicate that long ncRNAs can function as guides and tethers, and may be the molecules of choice for epigenetic regulation: First, unlike proteins and small RNAs, large ncRNAs remain tethered to the site of transcription, and can therefore uniquely direct allelic regulation. Second, ncRNAs command a much larger sequence space than proteins, and can therefore achieve very precise spatiotemporal control of development. These properties imply that long noncoding transcripts may ultimately rival small RNAs and proteins in their versatility as epigenetic regulators, particularly for locus- and allele-specific control.

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“…In a number of mammalian systems, allelic exclusion is triggered by the physical association of two allelic loci (Anguera et al 2006;Wutz and Gribnau 2007). We hypothesized that the rDNA arrays on the Drosophila X and Y chromosomes might interact, thereby directing silencing of the X chromosome rDNA array.…”

Section: Codominant Y Chromosomes Are Often Paired With the X Chromosomementioning

confidence: 99%

Nucleolar Dominance of the Y Chromosome in Drosophila melanogaster

Greil

Ahmad

2012

Genetics

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The rDNA genes are transcribed by RNA polymerase I to make structural RNAs for ribosomes. Hundreds of rDNA genes are typically arranged in an array that spans megabase pairs of DNA. These arrays are the major sites of transcription in growing cells, accounting for as much as 50% of RNA synthesis. The repetitive rDNA arrays are thought to use heterochromatic gene silencing as a mechanism for metabolic regulation, since repeated sequences nucleate heterochromatin formation in eukaryotes. Drosophila melanogaster carries an rDNA array on the X chromosome and on the Y chromosome, and genetic analysis has suggested that both are transcribed. However, using a chromatin-marking assay, we find that the entire X chromosome rDNA array is normally silenced in D. melanogaster males, while the Y chromosome rDNA array is dominant and expressed. This resembles "nucleolar dominance," a phenomenon that occurs in interspecific hybrids where an rDNA array from one parental species is silenced, and that from the other parent is preferentially transcribed. Interspecies nucleolar dominance is thought to result from incompatibilities between speciesspecific transcription factors and the rDNA promoters in the hybrid, but our results show that nucleolar dominance is a normal feature of rDNA regulation. Nucleolar dominance within D. melanogaster is only partially dependent on known components of heterochromatic gene silencing, implying that a distinctive chromatin regulatory system may act at rDNA genes. Finally, we isolate variant Y chromosomes that allow X chromosome array expression and suggest that the large-scale organization of rDNA arrays contribute to nucleolar dominance. This is the first example of allelic inactivation in D. melanogaster.

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X-Chromosome Kiss and Tell: How the Xs Go Their Separate Ways

Cited by 27 publications

References 76 publications

The X as Model for RNA's Niche in Epigenomic Regulation

The X as Model for RNA's Niche in Epigenomic Regulation

Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome

Nucleolar Dominance of the Y Chromosome in Drosophila melanogaster

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