X Inactivation and Epigenetics

DNA review our genetic information is encoded by the DNA double helix when DNA is read or transcribed one strand of the double helix serves as a template strand the specific order of the four bases encodes genetic information and serves as the blueprint for our genetic makeup each rung of the DNA ladder is called a base pair in total the human genome consists of about three billion base pairs and encodes about 30,000 genes in ourselves DNA is wrapped around proteins like thread around a spool the structure that we see here is called a nucleosome which consists of the DNA helix tightly coiled around histone proteins histones have long extensions called histone tails which protrude from the nucleosome core as we will see modifications to both the histone tails and the DNA itself are indicative of whether DNA is active or not and this is controlled by epigenetics epigenetics and the X chromosomes humans have 23 sets of chromosomes the sex chromosomes X&Y determine the sex of an individual females have two X chromosomes males have One X and one Y chromosome epigenetics refers to processes that instructor ourselves how and when to read the DNA blueprint as we will see female cells use an epigenetic mechanism to inactivate or silenced one of the X chromosomes in each cell to prevent abnormal development we are now looking at cells from a female body a full copy of the genome is found in the nucleus of every cell each cell has the same 23 pairs of chromosomes we can now see individual x chromosomes highlighted here are two x chromosomes from one cell the inactive X is compact in appearance whereas the active X occupies a much greater volume despite the two chromosomes having the same gene content we will now take a look at each X chromosome at the molecular level which is at approximately 1 million times magnification the active X chromosome the active chromosome has a dispersed or open appearance often described as resembling beads on a string molecules involved in gene transcription can access open DNA the active X chromosome has specific active histone tail modifications that tag the DNA in the next few shots we'll look at examples of molecules that can access the active X chromosome transcription factors can bind open DNA these proteins are important in transcription initiation they can recruit other proteins such as histone modifying enzymes a new modification is added to a histone tail open DNA is more loosely bound which allows for nucleus name disassembly nucleosome remodeling also access the active X chromosome these protein is slide the nucleus own along DNA ultimately these changes open the DNA and allow RNA polymerase the DNA reading enzyme to access and transcribe DNA into messenger RNA the inactive X chromosome [Music] the inactive x chromosome is more tightly bound and condensed than the active form this means that the DNA is less accessible to molecules involved in transcription inactive X has modifications including specific inactive histone tail modifications DNA methylation and additional structural proteins that help to zip up the DNA ultimately this compact version of the chromosome is unable to be transcribed and is therefore silenced so let's compare the two X chromosomes directly the active X has a dispersed or open appearance this means the genes on this chromosome are active or on the inactive X has a condensed or closed appearance meaning that the genes on this chromosome are inactive or off histone tail modifications and DNA methylation are examples of epigenetic marks modifications that distinguish between the active and inactive chromosomes epigenetic inheritance can be visualized by the process of X inactivation this is a close-up of a single cell from a 100 cell embryo an embryo which is approximately four days old at this early stage of development female embryos still have two active X chromosomes one X chromosome is inherited from their father the other is inherited from the mother around this time the two active X chromosomes interact transiently and one is inactivated the other is kept active this process is mediated by both RNAs and proteins the inactivation of the X chromosome involves the condensing of DNA this is marked by the change in histone tail modification the arrival of structural proteins which help condense the DNA and DNA methylation X inactivation is complete at the end of the 100 cell stage of embryo development the decision of which chromosome to inactivate is surprisingly random and individual cells can have either the maternal or paternal X chromosome remaining active however from this point on each cell will remember which X chromosome it has activated and passed this information on to its progeny as the embryo develops this is an example of epigenetic inheritance the same pattern is maintained into adulthood let's look at the female head out if we could visualize x-inactivation on the skin you would see a distinct pattern based on the growth and migration of the original hundred cells in the four-day-old embryo while it is not generally visible to the naked eye in humans you are probably familiar with this pattern as we see it regularly in calico cats in cats the gene that encodes coat color is found on the X chromosome as a result only female cats can inherit two different coat color genes if this happens she will exhibit that characteristic tortoiseshell coat because of X inactivation why is epigenetics important the epigenetic regulation of DNA is not peculiar to the X chromosome in fact it is used throughout the body to turn different genes on or off in different cell types for example the insulin gene is switched on in pancreatic cells where insulin is made but is inactive elsewhere in the body antibody genes are active in the antibody secreting plasma cells of the immune system but switched off elsewhere in the body and just as epigenetics is important for normal cell function when things go wrong it can lead to disease for example there are certain genes in our bodies that protect us from cancer collectively called tumor suppressor genes these genes are usually on some diseases can cause the aberrant inactivation of these suppressor genes which can lead to cancer scientists are trying to understand how epigenetic regulation controls normal development and how epigenetic mistakes heal by understanding the mechanisms involved in epigenetic control they will also start to look for new treatments that will override the epigenetic marks that cause disease [Music] you

Channel: WEHImovies

Views: 232,648

Rating: 4.9606075 out of 5

Keywords: Epigenetics, chromosome, inactivation, WEHI, Etsuko, Uno, Drew, Berry

Id: mHak9EZjySs

Length: 11min 3sec (663 seconds)

Published: Wed Jan 25 2012

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