X chromosome inactivation: How does it work?

In the previous post, it is discussed on how DNA can be modified and can change depending on external situations and how different combinations of factors can modify the genetic code. But it is imperative to discuss the main location of one of the central coding for mammals, and especially humans, and those are the chromosomes. Chromosomes as we know are very tight packets of DNA that contain the major building blocks of any organism. The chromosomes are then long strands of DNA that when combined can form any and all of the organisms in this world. But one chromosome in particular is very indicative to the creation of the organism in mammals, including humans, are the parent chromosomes, which in turn are the X chromosomes for mother, and Y chromosomes for the father. Within these chromosomes, it’s not surprising that the X chromosomes are the more important part of the pair, since it allows half of the set needed to form the embryo.

But it’s not as simple as it sounds. While it is commonly known that, when both chromosomes combine thanks to the sperm cells and the oocytes, both form the zygote that would replicate into a fetus, but there is also another step that is crucial for the genetic maintenance of the embryo, and that is X chromosome inactivation. Now, while it sounds redundant, it’s actually a very important process in the early stages of gestation of the zygote. X and Y chromosomes are crucial in the development of the sex of the fetus, since XX is for female and XY is for male. This is common knowledge, but there is more to it. In females, there has to be the process known as X chromosome inactivation.  In XCI, is creates a cellular complex that silences any excess genes, and since females have 2 X chromosomes, its highly important to “inactivate” the second chromosome in order to avoid any problems during the early stages of replication. In order to do that, it uses XIST (X inactivating specific transcript) in RNA to regulate the inactivation and maintain order within the transcription and replication process. The use of XIST in various sequences along the inactive X chromosome creates a series of epigenetic modifications that result in the formation of facultative heterochromatin. This chromatin then causes epigenetic modifications like histone modification and the previously mentioned DNA methylation. All this happens in the later stages in development of the zygote before the formation of the full fetus. And it’s important to note that, when it comes to males, there’s transcriptional silencing of the X chromosome which leads to the formation of the XY compound during late meiosis.

So, now that we know what it does and why its highly important, it’s easy to understand how this process is needed to avoid any genetic mishaps or deficiencies during the gestation period, due to not only existing genetic deficiencies that may cause syndromes due to no regulation (Klinefelter syndrome or Triple x syndrome) or have over regulation (Turner syndrome). These syndromes, already having some light genetic possibility, can be even further augmented by using and abusing drugs. These factors have been shown to increase these factors, and have been shown to increase a light change in the epigenetic effects and can cause further problems for their future young.

To further view these points, I recommend you read these papers that have studies on the most common recreational drugs and alcohol that show light on the subject:

·        X chromosome inactivation in women with alcoholism, by Manzardo AM, Henkhaus R, Hidaka B, Penick EC, Poje AB, Butler MG, retrievable here: https://www.ncbi.nlm.nih.gov/pubmed/22375556

·        X chromosome inactivation in Opioid Addicted Women, by Vousooghi N, Shirazi MS, Goodarzi A², Abharian PH, Zarrindast MR, retrievable here: https://www.ncbi.nlm.nih.gov/pubmed/26904175

And as always, please stay tuned to this blog to further your understanding of your genetic code, and you!