Dynamics of the Two Heterochromatin Types during Imprinted X Chromosome Inactivation in Vole Microtus levis

Evgeniya A Vaskova,Antonina I Zhelezova,Alexander I Shevchenko,Elena V Grigor'Eva,Suren M Zakian,Elena V Dementyeva,Sophia V Pavlova,John L Vandeberg,Robert Feil

doi:10.1371/journal.pone.0088256

Abstract

In rodent female mammals, there are two forms of X-inactivation – imprinted and random which take place in extraembryonic and embryonic tissues, respectively. The inactive X-chromosome during random X-inactivation was shown to contain two types of facultative heterochromatin that alternate and do not overlap. However, chromatin structure of the inactive X-chromosome during imprinted X-inactivation, especially at early stages, is still not well understood. In this work, we studied chromatin modifications associated with the inactive X-chromosome at different stages of imprinted X-inactivation in a rodent, Microtus levis. It has been found that imprinted X-inactivation in vole occurs in a species-specific manner in two steps. The inactive X-chromosome at early stages of imprinted X-inactivation is characterized by accumulation of H3K9me3, HP1, H4K20me3, and uH2A, resembling to some extent the pattern of repressive chromatin modifications of meiotic sex chromatin. Later, the inactive X-chromosome recruits trimethylated H3K27 and acquires the two types of heterochromatin associated with random X-inactivation.

Highlights

In mammals, there are three forms of X-chromosome inactivation (XCI) - meiotic, imprinted and random
We examined the dynamics of chromatin modifications associated with both types of Xi facultative heterochromatin in female trophoblast stem (TS) cells as well as preimplantation and postimplantation embryos of the common vole, Microtus levis
We studied modifications associated with the inactive chromatin at different stages of imprinted XCI in TS cells, as well as during spermatogenesis and early embryonic development of the common vole, M. levis

Summary

Introduction

There are three forms of X-chromosome inactivation (XCI) - meiotic, imprinted and random. The first form, meiotic sex chromosome inactivation (MSCI), occurs during spermatogenesis in eutherians and marsupials at the pachytene stage when all homologous chromosomes are paired with synaptonemal complexes. Heteromorphic X- and Y-chromosomes become transcriptionally inactive and form so-called sex or XYbody [1,2,3,4]. During imprinted XCI the paternally inherited X-chromosome is inactivated in all of the tissues of marsupials [6] and extraembryonic tissues (placenta, yolk sac) of some eutherians (e.g., rodents) [7,8,9]. Random XCI occurs in both embryonic and extraembryonic tissues in human [10]

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Conclusion