Reactivation of the inactive X chromosome in development and reprogramming

In mammals, one of the two X chromosomes of female cells is inactivated for dosage compensation between the sexes. X chromosome inactivation is initiated in early embryos by the noncoding Xist RNA. Subsequent chromatin modifications on the inactive X chromosome (Xi) lead to a remarkable stability of gene repression in somatic cell lineages. In mice, reactivation of genes on the Xi accompanies the establishment of pluripotent cells of the female blastocyst and the development of primordial germ cells. Xi reactivation also occurs when pluripotency is established during the reprogramming of somatic cells to induced pluripotent stem cells. The mechanism of Xi reactivation has attracted increasing interest for studying changes in epigenetic patterns and for improving methods of cell reprogramming. Here, we review recent advances in the understanding of Xi reactivation during development and reprogramming and illustrate potential clinical applications.     

Resetting epigenetic signatures to induce somatic cell reprogramming

Somatic cell reprogramming consists of the induction of a complex sequence of events that results in the modification of the developmental state of the cell. It is now routinely possible to reprogram fully differentiated cells back to pluripotent cells, and to transdifferentiate cells of a given type in cells of a totally different lineage origin. However, whether there are key initiating factors that are distinct from those that control stem-cell renewal and that can initiate the reprogramming process remains unknown. In contrast, what is clear is that, by modifying the epigenetic status of a cell, its reprogramming can be initiated. Here, we review the current literature that shows how the plasticity of a cell can be modulated by modifying its epigenetic status, and we discuss how epigenetic barriers can be removed, to induce an efficient reprogramming process.     

Finding the middle ground: how kinetochores power chromosome congression

Genomic stability requires error-free chromosome segregation during mitosis. Chromosome congression to the spindle equator precedes chromosome segregation in anaphase and is a hallmark of metazoan mitosis. Here we review the current knowledge and concepts on the processes that underlie chromosome congression, including initial attachment to spindle microtubules, biorientation, and movements, from the perspective of the kinetochore.     

Effect of cell proliferation on the condensation of the X chromosome in culture medium of the individual karyotype 49 XXXXX]

The influence of cell proliferation on the condensation of the X chromosome was observed in vitro in human fibroblasts with 49 XXXXX karyotype. The frequency of cells with four Barr-bodies is low during the logarithmic growth phase and increases to 80% when the cells are becoming confluent or, independently of cell contact, when cell growth is arrested in a medium with low serum content. The condensation of th X chromosomes is reversible when the cells start growing again in medium with a higher serum content.     

Distribution of sister chromatid exchanges in different types of chromatin in the X chromosome ofMicrotus cabrerae

We used the X chromosomes ofMicrotus cabrerae as a model to analyze the distribution of sister chromatid exchanges (SCEs) on different types of chromatin, because of the marked heterogeneity of the heterochromatin in the entire short arm and a portion of the long arm of this chromosome. Computer-simulated distributions, according to an algorithm that makes it possible to modify the distribution on the basis of any possible hypothesis, were compared with real distributions by log-linear models. We found that the frequency of SCEs in different types of heterochromatin was higher than that expected for a random distribution, and located an SCE hot-spot at the junction between euchromatin and heterochromatin. The possible relationship between the distribution of SCEs and base composition or chromatin accessibility are discussed.     

Robertsonian fusion leading to the formation of stable dicentric chromosome in an ascites cell line of the mouse

Summary The dicentric nature of a marker metacentric chromosome originated by robertsonian fusion has been established in the ascites cells of mouse sarcoma 180. C-banding analysis has revealed that the metacentric is actually a dicentric with 2 closely situated C-positive heterochromatic zones. The nature of the centromeres and the NF value of the cell indicate that this meta-dicentric marker has orginated by breakage and fusion within each of the short arms of 2 acrocentric chromosomes.Acknowledgment. Grateful acknowledgment is made to Dr N. Chatterji, former Director, CNCRC, Calcutta, for supplying the cell-line to the first author. Sincere thanks are due to Prof. Sujit K. Dasgupta, Head, Dept. of Zoology, H. M. Govt. College and to Dr A. K. Roy of the same department for encouragement.