Although male and female mammals have different reproductive organs, other organs, such as the heart and lungs, seem to be identical. However, when looking at the genes being expressed in male and female cells in any organ, there are substantial differences. Some of these are due to the fact that female cells have two X chromosomes and males have one X and one Y chromosome. In addition, the hormones produced by the gonads can influence the genes expressed. How these molecular differences are established and how they affect functionality is not known. The objective of this project is to investigate the molecular differences between male and female mice, starting soon after fertilization and throughout embryonic development by characterizing gene expression and epigenetic features at successive stages of embryogenesis. The data generated will allow comparative studies with other model organisms and lend insight into how evolution has shaped male and female genetic and hormonal differences. The project includes outreach and educational programs to increase awareness of how male and female physiologies differ among students, both at the graduate and undergraduate level. This project will also provide training opportunities for undergraduate hands-on research experiences. In addition, it will contribute towards creating a resource to train students to teach genomic and bioinformatic concepts to high school students in the area. These students are generally from underrepresented backgrounds, especially in the STEM disciplines.
Beginning soon after fertilization, the X and Y chromosomes program autosomal gene expression and the epigenomic landscape, establishing male- and female-specific gene networks. The mechanisms underlying these effects are unknown, as well as how male and female biases evolve across development and in different lineages. The objective of this project is to fill this knowledge gap by integrating experimental and systems level analyses in vitro and in vivo. It examines the hypothesis that regulatory factors encoded on the X and Y chromosomes dictate differential expression and epigenetic profiles of autosomal genes. Hormones equalize some of these differences, but others persist, affecting cellular phenotypes even in the adult organism. This hypothesis will be tested by: 1) determining the transcriptional and epigenetic effects of differentially expressed regulatory factors in early embryogenesis; and 2) identifing the biases in gene expression and epigenetic patterns dependent on the X and Y chromosomes before and after the appearance of gonadal hormones. These experiments will exploit a mouse model that allows segregation of the genetic and hormonal components of the male and female phenotypes. Since epigenetic marks established in early development can be latent and relevant to gene expression at later stages, this research will also serve as a paradigm for understanding how events in embryogenesis influence dimorphisms after birth and beyond. Moreover, these studies will lay the groundwork for mechanistic studies on the effects of transcription and epigenetic factor dosage on the transcriptome.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
