Epigenetics is an aspect of genetics which doesn’t always get as much attention as the study of DNA sequences. However, the function of DNA is impacted by the chemical modifications and structural changes that occur around DNA molecules. The study of that functional control is referred to as epigenetics. One example of this functional influence is X-chromosome inactivation (XCI). Here, we discuss the mechanisms and importance of XCI.

Most male mammals possess one X chromosome and females two, one from each parent. This creates a gene dosage dilemma. Having two active X chromosomes in females could lead to an imbalance in gene expression because they have two copies of every gene. The biological solution for this challenge is XCI. This epigenetic process randomly silences one of the two X chromosomes in each cell of a female’s body, effectively equalizing the gene expression between males and females. This process occurs early in embryonic development and is maintained throughout an individual’s life.

XCI is orchestrated primarily by a gene called Xist (X-inactive specific transcript) which encodes a long non-coding RNA (lncRNA) molecule. Xist RNA plays a pivotal role in silencing one of the X chromosomes by physically coating it. Early in a mammal organism’s embryonic development, while both X chromosomes are still active, each cell produces a small amount of a blocking factor molecule that blocks transcription of the Xist gene. However, this factor is manufactured in a very small amount, only sufficient to block the Xist gene on a single X chromosome. That X chromosome will remain active, while the Xist lncRNA begins the coating process on the other X chromosome, initiating a cascade of epigenetic events. These events include a series of histone methylation steps, eventually resulting in compaction of the inactivated X chromosome.

XCI is a random process; which X chromosome is inactivated is not predetermined and varies from one cell to the next. However, once an X chromosome is inactivated in a particular cell, it remains inactive and is passed on to all daughter cells. One visually striking example of the process is observed in the fur color pattern of calico cats. Calico cats are always female and their pair of X chromosomes bear genes which play a role in fur coloration. If the cat has one X chromosome which encodes the gene for orange fur and another X chromosome encoding black fur, then only one of those genes will continue to be expressed following the inactivation of one X chromosome. Since the process for selecting which of the two will be inactivated is random, the eventual distribution of color on the cat’s fur will also be random.

X-chromosome inactivation demonstrates the importance of epigenetics. Each of the two X chromosomes involved remains undamaged in terms of its DNA sequence, yet it has largely been deleted from the cell in a functional sense. In most cells, this effect is passed from the parent cell in which the inactivation first occurred, to all its daughter cells. This showcases the heritable nature of epigenetic changes, highlighting their significance in genetics and biology. As research in epigenetics continues to evolve, it is likely that we will discover even more intricate ways in which these epigenetic mechanisms influence our genes and, consequently, our lives.