The lesser known story of X-chromosome reactivation: A closer look into the reprogramming of the inactive X chromosome

X-chromosome inactivation (XCI) is an important mechanism employed by mammalian XX female cells to level X-linked gene expression with that of male XY cells. XCI occurs early in development as the pluripotent cells of the inner cell mass (ICM) in blastocysts successively differentiate into cells of all three germ layers. X-chromosome reactivation (XCR), the reversal of XCI, is critical for germ cell formation as a mechanism to diversify the X-chromosome gene pool. Here we review the characterization of XCR, and further explore its natural occurrence during development and the in vitro models of cellular reprogramming. We also review the key regulators involved in XCI for their role in suppressing the active histone marks and the genes in the active chromosome for their inhibition of X inactivation signals.Key words: X-chromosome reactivation, RNF12, reprogramming, primordial germ cells, iPS cellsX-chromosome inactivation (XCI) is an essential process occurring in female XX cells as a dosage compensation measure during development.¹ It ensures balanced X-chromosome-encoded proteins in male and female cells, and occurs randomly during early development, thus accounting for the mosaicism observed in female somatic cells. Once the cell has inactivated one of the X chromosomes, the pattern is maintained throughout the subsequent series of cell divisions. In mice, the paternal inactive X chromosome (Xi) is maintained throughout the early cleavage until the blastocyst stage, where cells of the inner cell mass (ICM) reactivate the inactive X chromosome.² At subsequent phases of early development, humans and mice share the pattern of XCI. Epiblast cells randomly inactivate one X chromosome, while the primordial germ cells (PGCs) reactivate the Xi during their migration to the genital ridges.^3–6 Interestingly, murine extra-embryonic trophoblast cells show non-random inactivation of the paternal X chromosome maintained in trophectoderm.^6,7 This pattern is, however, not conserved, as human trophectoderm cells randomly inactivate the paternal or maternal X chromosome. In addition to the PGCs and early developing embryo, cells cultured under defined conditions or undergoing reprogramming show X-chromosome reactivation (XCR).⁸ XCI has been extensively studied, while XCR is not well-understood, mainly due to the lack of easily accessible models. Here, we will review the developmental process of XCR and molecular mechanism involved in XCI and XCR.     

2009 Society for Medical Anthropology Conference: Global Public Health through the Eyes of Medical Anthropologist Didier Fassin

At the 2009 Society for Medical Anthropology Conference at Yale University, anthropologist Didier Fassin discussed social inequality and the politicization of health in the context of global public health.U.S. Rep. Joe Wilson shouted, “You lie!” during President Obama’s denial that the proposed health care reform bill would cover illegal immigrants, and anthropologist Didier Fassin used that antagonistic stance toward what the 1978 Declaration of Alma-Ata [1] had called a fundamental human right to best illustrate the issues of social inequality and the politicization of health.Global public health was one focus of the 2009 Society for Medical Anthropology Conference at Yale University in September. Since its inception in 1948, the World Health Organization (WHO) has striven to provide health assistance to the world population, especially those in developing countries. But Fassin, professor of social science at the Institute for Advanced Study at Princeton, professor of sociology at the Université de Paris, Nord, and director of studies in political and moral anthropology at the Ecole des Hautes Études en Sciences Sociales, argued that the concept of global health, albeit well-meaning, is problematic. Its utopian nature is clearly apparent in the rhetoric of politicians, he said, adding that health as a gift of nature, a common good, and the core of the WHO, quickly becomes an object of politics and the coverage in times of sickness of a select few is akin to entitlement and privilege.The present age of globalization certainly makes health threats such as epidemics a threat to all, and nations are in it together to take preventive measures or put up a concerted fight. However, threats like bioterrorism or predicted consequences of global warming such as population migration may be viewed, particularly by Western countries, as security issues that menace national interests and state sovereignties. The consequence being that new policies are implemented that may directly or indirectly affect the rest of the world population.And then there is the issue of humanitarian intervention, which Fassin refers to as “politics of life” [2]. How can we view humanitarianism with the eye of a cynic when it is, in essence, the effort to demonstrate the very best of our nature? Yet the transformation of some humanitarian interventions into military operations and the decision to intervene (Iraq, Kosovo, Bosnia) or not (Rwanda, Ethiopia, Cambodia), politicize this notion. Additionally, Fassin believes that the key nation-states integrate their own cultural and political biases during interventions in troubled regions.Nowhere is this subjectivity more apparent than in the image of suffering as depicted by psychologists and psychiatrists working for non-government organizations (NGOs). NGOs compile testimonies of traumatized people in war and conflict zones, but their subjective narratives enmeshed in the diagnosis reports are increasingly supplanting faithful witness accounts. Fassin sees this trauma as “political expression of the world” [3]. The experts, in trying to raise awareness on issues that need immediate attention, may dramatize certain situations or get emotionally involved during their missions and take sides. They become the new voice of the conflict and their efforts may throw the victims into a state of confusion.It’s no surprise then that some nations view with distrust Western practices and their portrayal of aggressors and victims [4]. In 2000, Thabo Mbeki, then president of South Africa, convened an advisory panel that aimed to collect scientific data to prove that HIV does not cause AIDS. In return, he received the Durban Declaration with the signatures of more than 5,000 scientists and doctors who unilaterally declared the opposite to be scientifically true.Fassin brings up the abovementioned issues in order to shift attention to the difficulties that face our common efforts for better health services. It is truly challenging for Western leaders to mend the rift between their political agendas and accessible health for all, and as long as that continues to be the case, health care will elude millions.