Read More
Date: 20-12-2015
4666
Date: 16-3-2021
1546
Date: 1-1-2016
2093
|
Barr Body
In eutherian (placental) mammals, dosage compensation mechanisms operate in female cells to silence one of the two X-chromosomes, so that female cells have as many X-chromosome-derived transcripts as male cells containing a single X-chromosome. This X-chromosome inactivation process was first proposed by Mary Lyon (1961) and is known as the Lyon hypothesis (1). Female mammalian embryos begin development with two active X-chromosomes, but very early in embryogenesis almost all of the genes on one of the two X-chromosomes become inactivated Random X-Inactivation). Although the initial choice between inactivation of the maternal or paternal X-chromosome is random, once established in a repressed state the same X-chromosome are inactivated after every cell division. The inactivation process occurs over the entire chromosome, and practically all of the genes on the chromosome are silenced. This transcriptional inactivation is concomitant with the chromosome taking on the appearance of heterochromatin and also becoming late replicating during S phase. Only a small fraction of the inactive X-chromosome, including the genes located in the pseudoautosomal region at Xp22.3, escapes the global silencing process (2). The inactive chromosome remains in the nucleus and can be detected cytologically as a Barr body in somatic cells (3). The Barr body is found only in cells containing more than one X-chromosome, if cells are trisomic for the X-chromosome, two Barr bodies will be detected. The staining procedures used to detect Barr bodies argue for a global difference in chromatin condensation (4). Differences in staining of heterochromatin compared to transcriptionally competent euchromatin may be caused by differences in compaction or differences in the association of many more accessory proteins in heterochromatin (5).
The use of advanced microscopy and molecular cytogenetics, in which fluorescent in situ hybridization is used to “paint” chromosomal territories, has recently allowed detailed dissection of chromosomal organization. Light microscopic optical serial sectioning of the active and inactive X-chromosome territories reveal that they occupy similar volumes. However, reconstructed active X-chromosomes have a flatter shape and a more extended, folded surface area than the inactive X-chromosome (6). The conclusion is that the differential staining properties of the Barr body are caused mainly by the association of a distinct group of accessory proteins and RNA with this inactive chromosome.
Even on the active X-chromosome, most of the chromatin is not transcriptionally active. Thus, on both the inactive and the active X-chromosomes, the great majority of the chromatin is maintained in a folded state typical of a transcriptionally repressed state. There are, however, global differences in chromatin organization between active and inactive X-chromosomes. The inactive X chromosome has high overall nucleosomal density—i.e., it carries a higher “concentration” of all histones, including the unusual variant macroH2A, than all autosomes or the active X (7). This likely contributes to the optical density of the Barr Body as visualized microscopically. The Barr body contains methylated DNA, hypoacetylated histones, a specialized structural RNA (Xist), and is late replicating during the S phase. Association with Xist RNA is an important causal factor in X-inactivation, and somehow leads to the selective hypermethylation of the inactive X, which results in deacetylation of chromatin assembled over it and transcriptional quiescence. The three-dimensional distribution in the nucleus of Xist RNA coincides with the chromosomal territory occupied by the inactive X-chromosome (8). Even after removing bulk chromatin in the preparation of a nuclear matrix (which is responsible for the overall morphology of the nucleus), the Xist RNA remains in the matrix. This is consistent with the hypothesis that Xist RNA has a structural role in establishing the inactive X-chromosome territory. The Barr body still has a great deal to teach scientists about the molecular mechanisms that establish and maintain nuclear compartments.
References
1.M.F. Lyon, Nature 190, 372–373 (1961).
2.C.M. Disteche, Trends Genet. 11, 17–22 (1995).
3.M.L. Barr and E.G. Bertram, Nature 163, 676–677 (1949).
4.S.M. Gartler and A.D. Riggs, Annu. Rev. Genet. 17, 155–190 (1983. (
5.S.W. Brown, Science 151, 417–425 (1966).
6.R. Eils et al., J. Cell Biol. 135, 1427–1440 (1996. (
7.Perche P.Y. et al., Curr. Biol. 10, 1531–1534 (2000).
8.C.M. Clemson, J.A. McNeil, H.F. Willard, and J.B. Lawrence J. Cell Biol. 132, 259–275 (1996).
|
|
علامات بسيطة في جسدك قد تنذر بمرض "قاتل"
|
|
|
|
|
أول صور ثلاثية الأبعاد للغدة الزعترية البشرية
|
|
|
|
|
مكتبة أمّ البنين النسويّة تصدر العدد 212 من مجلّة رياض الزهراء (عليها السلام)
|
|
|