X-chromosome inactivation in the early mouse embryo Inner cell mass Extraembryonic tissue of placenta Embryonic cells Extraembryonic The lacz reporter gene has been fused to 1 X-chromosome( paternal )in this precursors female XX mouse embryo(C, D) The paternally derived X chromosome con- tained a lacz transgene that is active in the early embryo. Those cells in which the chromosome is active make B-galactosidease and can be stained blue. The other cells are counterstained and appear pink. C) In the early blastocyst stage at day 4, both X chromo- random inactivation of one of the chromosomes occurs. Thuys gi somes are active in all cells; thus all cells appear blue. (D)At da those where the paternal X is active stain blue. In the mouse(but not the human) trophoblast, the paternally derived X chromosome in preferentially inactivated Thus, the trophoblast cells are uni- lly pink. (A, B, photographs courtesy of M. L. Barr; C, D after Sugimoto et al. 2000, photographs courtesy of N. Takagi
X-chromosome inactivation in the early mouse embryo The lacZ reporter gene has been fused to 1 X-chromosome ( paternal ) in this female XX mouse embryo ( C, D)
The XIST RNA chromatin complex is triggering other mechanisms for inactivating the X-chromosome. Various promoters are methylated and the chromatin structure becomes condensed via histone modifications like methylation and deactylation. This nucleosome changes are leading then to the formation of heterochromatin occuring as Barr bodies (A) Attributes of the inactive x chromosome XIST RNA Production XIST/Barr body complex Histone H4 hypoacetylation Histone H3 methylation Histone macroH2AI concentration Nuclear envelope association Late replication Heterochromatin Methylated promoters Figure 5.24 The inactive x chromosome of human female cells contains underacetylated histone H4.(A) Mouse XIST RNA( red)on an Chromosomes from a human female fibroblast ell stained green with fluorescent antibody to inactive X-chromosome( blue) acetylated histone H4. while all the other chro- mosomes are stained green, the inactive X is not and thus appears red (arrow). (B)List of On the active x-chromosome attributes characterizing the inactive X chro- mosome (From Jeppesen and Turner 1993; the promoter for XIST is photograph courtesy of the authors. methylated and so inactive
Mouse XIST RNA ( red ) on an inactive X-chromosome ( blue) . On the active X-chromosome the promoter for XIST is methylated and so inactive The XIST RNA chromatin complex is triggering other mechanisms for inactivating the X-chromosome . Various promoters are methylated and the chromatin structure becomes condensed via histone modifications like methylation and deactylation . This nucleosome changes are leading then to the formation of heterochromatin occuring as Barr bodies
The later inactive X-chromosome transcribes a rna which does not code a protein= XIST. XIST is interacting with the chromosomal chromatin, forming the XIsT Barr body complex RNA staining of Xx chromosomes in murine embryonic stem cells. Red= X linked phosphoglycerate kinase(PgK), Blue= XIST B)In the early stage of development both X-chromosomes transcribe PgK and XIsT. c)In one chromosome the XIST is stabilized and this chromosome does not transcribe pgK anymore. D)After the cell finished differentiation one chromosome only transcribes XIst and no PgK anymore and the other X-chromosome only transcribes PgK and no XIsT anymore
The later inactive X-chromosome transcribes a RNA which does not code a protein = XIST . XIST is interacting with the chromosomal chromatin , forming the XIST Barr body complex RNA staining of XX chromosomes in murine embryonic stem cells . Red = Xlinked phosphoglycerate kinase (PgK), Blue = XIST B) In the early stage of development both X-chromosomes transcribe PgK and XIST . C) In one chromosome the XIST is stabilized and this chromosome does not transcribe PgK anymore . D) After the cell finished differentiation one chromosome only transcribes XIST and no PgK anymore and the other X-chromosome only transcribes PgK and no XIST anymore
1. Very early in the development of female mammals, both Paternal X chromosomes are active chromosome AT FERTILIZATION 2. As development proceeds, one X chromosome is inacti ale zygote with X chromosomes % vated in each cell Maternal X chromosome 3. This inactivation is random. In some cells, the paternally derived x chromosome is inactivated; in other cells, the EARLY CLEAVAGE maternally derived X chromosome is shut down Both X chromosomes active in all cells 4. This process is irreversible. Once an X chromosome has (3 been inactivated in a cell. the same X chromosome is in activated in all that cell s progeny. Since X inactivation happens relatively early in development, an entire region IMPLANTATION of cells derived from a single cell may all have the same X Random inactivation chromosome inactivated. Thus, all tissues in female of one x chromosom in all cells of the inner mammals are mosaics of two cell types ell mass, which will Barr bodies Barr body in the nucleus of a human oral epithelial cell stained with Cresyl violet
Barr body in the nucleus of a human oral epithelial cell stained with Cresyl violet