Dr Elsie Jacobson grew up in Aotearoa/NZ, completing her BSc(hons) in genetics at the University of Otago. She pursued her doctoral studies at the Liggins Institute, University of Auckland, investigating the impacts of mechanical stress on chromatin conformation and transcription under the supervision of Dr Justin O’Sullivan. She is currently doing her Postdoc with Dr Kathrin Plath at the University of California Los Angeles (UCLA), with a focus on X inactivation in placental development and disease.
In placental mammals, females have two X chromosomes while males only have one. X chromosome inactivation (XCI) is a dosage compensation mechanism to silence genes on one of two X chromosomes in females, equalizing gene expression between the sexes. XCI is orchestrated by the long non-coding RNA Xist, which recruits repressive proteins via its repeat sequence elements. To understand the role of sex chromosome dosage compensation in development, we generated a mouse model of incomplete X-linked gene silencing. We found that increased X-linked gene dosage in the placenta causes defects at the feto-maternal interface, causing growth restriction and in utero lethality. We hypothesize that X-linked gene dosage imbalance causes similar defects in mouse interspecies hybrids, providing a key role for XCI in mammalian speciation. Our work provides a novel perspective on balancing gene expression from active and inactive X chromosomes, and insight into the role of X-linked dosage compensation in placental development, disease, and evolution.