Jeannie Lee (Harvard) 1 - X Chromosome Inactivation: Making and Breaking the Silence
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- เผยแพร่เมื่อ 31 พ.ค. 2024
- www.ibiology.org/development-...
The X chromosome is many time larger than the Y chromosome. To compensate for this genetic inequality, female mammalian cells undergo X chromosome inactivation of one X chromosome. Dr. Jeannie Lee explains the how and why of X chromosome inactivation.
Talk Overview:
In mammals, sex is determined by a pair of unequal sex chromosomes. Genetically male mammals have an X and a Y chromosome while genetically female mammals have two X chromosomes. The X chromosome is many times larger than the Y chromosome. To compensate for this genetic inequality, female mammals undergo X chromosome inactivation in which one of the X chromosomes is randomly chosen to be silenced. X chromosome inactivation has been studied for over 50 years both because it is a physiologically important event and because it is an excellent model for studying epigenetic silencing of genes by long non-coding RNAs. In her first talk, Dr. Jeannie Lee gives an overview of the steps a cell must go through during X inactivation. These include “counting” the X chromosomes, deciding which X chromosome to inactivate, initiating the inactivation and spreading it across the chromosome, and finally maintaining inactivation of the same X chromosome for the rest of the life of the organism.
In her second talk, Lee elaborates on the early steps of X inactivation. Very early in development, cells “count” the number of X chromosomes and decide if one needs to be inactivated, and if so which one. There is a region of the X chromosome called the X inactivation center which is enriched in long non-coding RNAs (lncRNAs). Lee explains how she and others showed that by sensing the ratio of two specific lncRNAs the cell can determine how many X chromosomes are present. Further studies showed that two different lncRNAs are responsible for randomly determining which X chromosome will be inactivated. Finally, she discusses the hypothesis that the allelic choice mechanism depends on a transient chromosomal pairing event that occurs at the beginning of the dosage compensation process.
And in her last talk, Lee describes how X inactivation is nucleated and spreads across the X chromosome. The Xist lncRNA is known to be necessary and sufficient for X inactivation. Lee describes experiments that identified the factors that tether Xist to the X chromosome and showed how Xist spreads to cover the entire X chromosome. She then goes on to explain that Xist blocks transcription in three ways: 1) Xist recruits factors that repress transcription via epigenetic modification such as histone methylation 2) Xist repels factors that open chromatin preparing it for transcription and 3) Xist changes the 3 dimensional organization of chromosomes. Lee ends with a model of our current understanding of the complex but critical process of X chromosome inactivation.
Speaker Biography:
Dr. Jeannie Lee is a Professor in the Department of Genetics at Harvard Medical School and in the Department of Molecular Biology at Massachusetts General Hospital (MGH). Her lab uses X chromosome inactivation as a model to study epigenetic regulation by long noncoding RNAs.
Lee received her AB in biochemistry and molecular biology from Harvard University and her MD/PhD from the University of Pennsylvania School of Medicine. She was a postdoctoral fellow at the Whitehead Institute and a resident at MGH before joining Harvard/MGH as a faculty member in 1997. Lee was also an HHMI Investigator from 2001-2018. She is a member of the National Academy of Sciences and a Fellow of the American Association for the Advancement of Science. Lee has been honored with numerous awards including the 2016 Centennial Prize from the Genetics Society of America, the 2016 Lurie Prize from the Foundation for the National Institutes of Health, and the 2010 Molecular Biology Award from the National Academy of Sciences. In 2018, she was President of the Genetics Society of America.
Learn more about Dr. Lee’s research here: www.x-inactivation-lee-lab.org - วิทยาศาสตร์และเทคโนโลยี
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A super lecture, very well presented. Thanks Jeannie Lee and iBiology!
What an amazing lecture!!
This channel is amazing
Absolutely
Great lecture . I always maintained that junk DNA is a false statement of incomplete scientific knowledge. Of interest is if increase in gene expression requires a fine tuning expression , in other words is overexpression of a particular gene beneficial and chronologically determinant.
Hello, how could we say in the X-linked inheritance that there is a carrier or pure form if the second x chromosome is inactivated anyway and how the presence of one x chromosome would affect if always the only one X is activated.
fascinatiing. When you say that this is something that all mammals do, am i correct in assuming that this does not happen in non mammals, for example, reptiles? if so, why?
Very nice
expected to learn more on Mary Lyon's experiments that led her to this groundbreaking conclusion, someone please let me know any source to learn about that!
Hello mam
My question is, the inactivation of x chromosome have any effect on autosomal genes?
thank you
I find this lecture really informing. I have one from of intersex. During gestation my germ cells failed to fully reach the gonads. Thus one gonad remained as a fetal gonad, ovotestis and an attached germ cell teratoma. Depending on how you define it.
My other gonad did develop as a testis but remain small and immature.
If that were not enough I have a number of germ cell teratoma found in various areas of my abdomen. Two were removed when I was ten years old and several others were found when I was an adult. These teratoma were 10 cm and 17.5 cm when surgically remove. The 10 cm one happened to also be malignant.
I tend to be asexual but also see myself as being transgender.
@Ismael barrera Interesting! I’ll have to digest this information and do more study
If you reactive the inactive X, will it also inactive the previously active X? otherwise wouldn’t it lead imbalance and cause other problems?
My name is Jeannie
Hmmmm. If inactivation turns us basically into Turners, why do Turners have a recognizable condition? Or they turn off that one by mistake in some cells?
Because there’s control mechanisms, the inactivated X is not turned useless, it is still used to control/balance the active X
severe phenotype character are seen in turners due to deficiency in escape genes from silencing.
Not all genes are silenced on the inactive X. A bunch of genes escape inactivation.
It’s not all inactive still 10% xicst rna but which one gets inactived israndom and it happens in mammals for dosage compensation
Does anyone know which x passes down to germ cell during meiosis in females and how this process is reversed
Then how are females safe from X linked or sexlinked diseases if this phenomenon occurs?
What happens then?
Females can still be affected by X linked diseases but it’s a little more tricky than it seems. If it’s a dominant condition and the affected X is active, the disease will be present; if it’s a recessive condition (only presents in homozygous) then the other unaffected X can compensate for it, and if it’s the unaffected X that’s active the disease will not be present.
@@bearpancakes so in a recessive condition if the unaffected X is silenced then the disease will be present, yea?
I had the same question, particularly with regard to color-blindness, which, as I understand it, is a X-linked recessive condition. The best explanation that I could come up with in view of what was presented in this lecture, was in terms of the random “mosaic” of activation in the cells of a female. So consider a female having two X-chromosomes, one of which carries the allele for colorblindness and the other carries the normal allele. Because the cells in the female will be a “mosaic” composed of cells in which either one of the X-chromosomes is inactive, about half the cells will have the X-chromosome with the normal allele as the active one, staving off color-blindness (and similarly other X-chromsome linked recessive conditions). Fascinating lecture, but as in much of Biology, generated more questions than it answered!
"there are no supernumerary Xes" - with some excepions ;)
What about intersex?
Which definition are you talking about?
That why you not advanced in genitc and u will never be until understanding the polarities of these jens
First it's not y x. It's h and small x for what we gain from eating that is important to live your so wrong and I proud to tell