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1.
Intersection of the RNA interference and X-inactivation pathways 总被引：1，自引：0，他引：1
In mammals, dosage compensation is achieved by X-chromosome inactivation (XCI) in the female. The noncoding Xist gene initiates silencing of the X chromosome, whereas its antisense partner Tsix blocks silencing. The complementarity of Xist and Tsix RNAs has long suggested a role for RNA interference (RNAi). Here, we report that murine Xist and Tsix form duplexes in vivo. During XCI, the duplexes are processed to small RNAs (sRNAs), most likely on the active X (Xa) in a Dicer-dependent manner. Deleting Dicer compromises sRNA production and derepresses Xist. Furthermore, without Dicer, Xist RNA cannot accumulate and histone 3 lysine 27 trimethylation is blocked on the inactive X (Xi). The defects are partially rescued by truncating Tsix. Thus, XCI and RNAi intersect, down-regulating Xist on Xa and spreading silencing on Xi. 相似文献
2.
Role of histone H3 lysine 27 methylation in X inactivation 总被引：1，自引：0，他引：1
Plath K Fang J Mlynarczyk-Evans SK Cao R Worringer KA Wang H de la Cruz CC Otte AP Panning B Zhang Y 《Science (New York, N.Y.)》2003,300(5616):131-135
The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi. 相似文献
3.
Molecular coupling of Xist regulation and pluripotency 总被引：2，自引：0，他引：2
Navarro P Chambers I Karwacki-Neisius V Chureau C Morey C Rougeulle C Avner P 《Science (New York, N.Y.)》2008,321(5896):1693-1695
During mouse embryogenesis, reversion of imprinted X chromosome inactivation in the pluripotent inner cell mass of the female blastocyst is initiated by the repression of Xist from the paternal X chromosome. Here we report that key factors supporting pluripotency-Nanog, Oct3/4, and Sox2-bind within Xist intron 1 in undifferentiated embryonic stem (ES) cells. Whereas Nanog null ES cells display a reversible and moderate up-regulation of Xist in the absence of any apparent modification of Oct3/4 and Sox2 binding, the drastic release of all three factors from Xist intron 1 triggers rapid ectopic accumulation of Xist RNA. We conclude that the three main genetic factors underlying pluripotency cooperate to repress Xist and thus couple X inactivation reprogramming to the control of pluripotency during embryogenesis. 相似文献
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Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic 总被引：1，自引：0，他引：1
Augui S Filion GJ Huart S Nora E Guggiari M Maresca M Stewart AF Heard E 《Science (New York, N.Y.)》2007,318(5856):1632-1636
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Mammalian X inactivation turns off one female X chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing. 相似文献
7.
The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene 总被引：1，自引：0，他引：1
The Xist noncoding RNA is the key initiator of the process of X chromosome inactivation in eutherian mammals, but its precise function and origin remain unknown. Although Xist is well conserved among eutherians, until now, no homolog has been identified in other mammals. We show here that Xist evolved, at least partly, from a protein-coding gene and that the loss of protein-coding function of the proto-Xist coincides with the four flanking protein genes becoming pseudogenes. This event occurred after the divergence between eutherians and marsupials, which suggests that mechanisms of dosage compensation have evolved independently in both lineages. 相似文献
8.
Cao R Wang L Wang H Xia L Erdjument-Bromage H Tempst P Jones RS Zhang Y 《Science (New York, N.Y.)》2002,298(5595):1039-1043
Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax (Ubx) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing. 相似文献
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非编码KNAXist介导的X染色体失活是表观遗传研究的一个典范,该系统能使一整条染色体变为异染状态。从Xist与X染色体计数、失活的选择、失活的起始和失活的维持等方面综述了其分子机制。 相似文献
11.
M A Goldman K R Stokes R L Idzerda G S McKnight R E Hammer R L Brinster S M Gartler 《Science (New York, N.Y.)》1987,236(4801):593-595
Mammalian X-chromosome inactivation involves a coordinate shutting down of physically linked genes. Several proposed models require the presence of specific sequences near genes to permit the spread of inactivation into these regions. If such models are correct, one might predict that heterologous genes transferred onto the X chromosome might lack the appropriate signal sequences and therefore escape inactivation. To determine whether a foreign gene inserted into the X chromosome is subject to inactivation, transgenic mice harboring 11 copies of the complete, 17-kilobase chicken transferrin gene on the X chromosome were used. Male mice hemizygous for this insert were bred with females bearing Searle's translocation, an X-chromosome rearrangement that is always active in heterozygous females (the unrearranged X chromosome is inactive). Female offspring bearing the Searle's translocation and the chicken transferrin gene had the same amount of chicken transferrin messenger RNA in liver as did transgenic male mice or transgenic female mice lacking the Searle's chromosome. This result shows that the inserted gene is not subject to X-chromosome inactivation and suggests that the inactivation process cannot spread over 187 kilobases of DNA in the absence of specific signal sequences required for inactivation. 相似文献
12.
Vernalization is an environmentally-induced epigenetic switch in which winter cold triggers epigenetic silencing of floral repressors and thus provides competence to flower in spring. In Arabidopsis, winter cold triggers enrichment of tri-methylated histone H3 Lys(27) at chromatin of the floral repressor, FLOWERING LOCUS C (FLC), and results in epigenetically stable repression of FLC. This epigenetic change is mediated by an evolutionarily conserved repressive complex, polycomb repressive complex 2 (PRC2). Here, we show that a long intronic noncoding RNA [termed COLD ASSISTED INTRONIC NONCODING RNA (COLDAIR)] is required for the vernalization-mediated epigenetic repression of FLC. COLDAIR physically associates with a component of PRC2 and targets PRC2 to FLC. Our results show that COLDAIR is required for establishing stable repressive chromatin at FLC through its interaction with PRC2. 相似文献
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Arabidopsis thaliana accessions have adapted to growth in a wide range of climates. Variation in flowering and alignment of vernalization response with winter length are central to this adaptation. Vernalization involves the epigenetic silencing of the floral repressor FLC via a conserved Polycomb (PRC2) mechanism involving trimethylation of Lys(27) on histone H3 (H3K27me3). We found that variation for response to winter length maps to cis polymorphism within FLC. A rare combination of four polymorphisms localized around the nucleation region of a PHD-Polycomb complex determines a need for longer cold. Chromatin immunoprecipitation experiments indicate that these polymorphisms influence the accumulation of H3K27me3 in Arabidopsis accession Lov-1, both at the nucleation site and over the gene body. Quantitative modulation of chromatin silencing through cis variation may be a general mechanism contributing to evolutionary change. 相似文献
15.
To achieve X-chromosome dosage compensation, organisms must distinguish X chromosomes from autosomes. We identified multiple, cis-acting regions that recruit the Caenorhabditis elegans dosage compensation complex (DCC) through a search for regions of X that bind the complex when detached from X. The DCC normally assembles along the entire X chromosome, but not all detached regions recruit the complex, despite having genes known to be dosage compensated on the native X. Thus, the DCC binds first to recruitment sites, then spreads to neighboring X regions to accomplish chromosome-wide gene repression. From a large chromosomal domain, we defined a 793-base pair fragment that functions in vivo as an X-recognition element to recruit the DCC. 相似文献
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Willingham AT Orth AP Batalov S Peters EC Wen BG Aza-Blanc P Hogenesch JB Schultz PG 《Science (New York, N.Y.)》2005,309(5740):1570-1573
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The Maternal-Effect Sterile (MES) proteins are essential for germline viability in Caenorhabditis elegans. Here, we report that MES-4, a SET-domain protein, binds to the autosomes but not to the X chromosomes. MES-2, MES-3, and MES-6 are required to exclude MES-4 and markers of active chromatin from the X chromosomes. These findings strengthen the emerging view that in the C. elegans germ line, the X chromosomes differ in chromatin state from the autosomes and are generally silenced. We propose that all four MES proteins participate in X-chromosome silencing, and that the role of MES-4 is to exclude repressors from the autosomes, thus enabling efficient repression of the Xs. 相似文献
19.
随着基因组测序等生物技术的进步和发展,越来越多的非编码RNA被发现,并且其功能也被逐渐鉴定出来.目前研究编码RNA已经是当前生命科学研究的前沿热点,这些小分子RNA存在于几乎所有高等的真核生物细胞中,对生物具有非常重要的调控功能.简要介绍了ncRNA的研究进展. 相似文献
20.
Parisi M Nuttall R Naiman D Bouffard G Malley J Andrews J Eastman S Oliver B 《Science (New York, N.Y.)》2003,299(5607):697-700
Sex chromosomes are primary determinants of sexual dimorphism in many organisms. These chromosomes are thought to arise via the divergence of an ancestral autosome pair and are almost certainly influenced by differing selection in males and females. Exploring how sex chromosomes differ from autosomes is highly amenable to genomic analysis. We examined global gene expression in Drosophila melanogaster and report a dramatic underrepresentation of X-chromosome genes showing high relative expression in males. Using comparative genomics, we find that these same X-chromosome genes are exceptionally poorly conserved in the mosquito Anopheles gambiae. These data indicate that the X chromosome is a disfavored location for genes selectively expressed in males. 相似文献