Xist (X-inactive specific transcript) plays a crucial role in X-inactivation. This non-coding RNA becomes upregulated on the X chromosome that is to be inactivated upon differentiation. Previous studies have revealed that although maintenance-type DNA methylation is not essential for X-inactivation to occur, it is required for the stable repression of Xist in differentiated cells. However, it is unknown whether differential de novo methylation at the Xist promoter, which is mediated by Dnmt3a and/or Dnmt3b, is a cause or a consequence of monoallelic expression of Xist. We show that Xist expression is appropriately regulated in the absence of Dnmt3a and Dnmt3b and that a single X chromosome undergoes proper inactivation in mutant females. Our results indicate that a mechanism(s) other than DNA methylation plays a principal role in initiating X-inactivation. We also demonstrate that delayed upregulation of Xistdoes not induce X-inactivation, consistent with a crucial developmental window for the chromosomal silencing.
History of our journals
As our publisher, The Company of Biologists, turns 100 years old, read about Development’s journey and highlights from some its first issues, and explore the history of each of our sister journals: Journal of Cell Science, Journal of Experimental Biology, Disease Models & Mechanisms and Biology Open.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues
Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology
In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
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