by Researchers at Massachusetts General Hospital (MGH) have uncovered intriguing insights into the silencing of X chromosome genes passed on from fathers to daughters. The study, published in Molecular Cell, sheds light on the intricate mechanisms balancing X-linked gene activity between the sexes during embryo development and over evolutionary timescales.
Daughters inherit one X chromosome from their mother and one from their father, while sons receive their single X chromosome from their mother. The study reveals that a significant portion of the X chromosome passed on from fathers to daughters is inherently silent even before fertilization, suggesting a sophisticated mechanism for maintaining gene dosage balance between the sexes.
Analyzing gene expression patterns in mouse embryos, the researchers observed that some genes from the paternal X chromosome undergo new inactivation during female embryo development, consistent with previous findings. However, they also discovered a novel phenomenon where certain genes inherited from the father are pre-suppressed, particularly those with greater evolutionary age on the X chromosome.
Lead author Jeannie T. Lee, MD, Ph.D., elucidates that this ancient mechanism ensures equal distribution of X chromosome genes in sons and daughters during embryogenesis, preventing potential disadvantages for male embryos. Co-author Chunyao Wei, Ph.D., highlights the critical control required for these pre-silenced genes in embryos to avoid X-gene overdosage in daughters.
Furthermore, the study uncovers a complex interplay between the maternal and paternal X chromosomes, with maternal X chromosome genes being modulated to maintain balance with the rest of the genome. Lee and her team found a coordinated upregulation of genes on the maternal X chromosome alongside silencing of genes on the paternal X chromosome during female embryo development, indicating a delicate equilibrium to prevent dominance by other chromosomal pairs.
In essence, the dynamic regulation of X chromosome gene expression from fathers to daughters represents a finely tuned process that underpins developmental equilibrium across sexes. The findings offer new perspectives on the intricate mechanisms governing genetic inheritance and reproductive biology, with implications for understanding sex chromosome evolution and gene dosage control in embryos.
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