Howard Chang (Stanford, HHMI) 2: LncRNA Function at the RNA Level: Xist

In this talk, Dr. Howard Chang describes epigenomic approaches pioneered by his lab and the role of long-noncoding RNAs (lncRNAs) in regulating gene expression.

In Part 1 of this series, Dr. Howard Chang introduces epigenomics, the study of DNA regulatory mechanisms that determine which genes are turned on or off in cells at specific times. The epigenome integrates signals from the environment to modify expression of the DNA blueprint inherited from an individual’s parents. Chang’s lab has pioneered techniques to map the landscape of chromatin, the complex of DNA, RNA and protein that organizes the genome and regulates gene expression. One example is ATAC, the Assay of Transposase Accessible Chromatin, which uses a bacterial transposase to mark open chromatin and identify genes that are likely turned “on”.

In his Part 2, Chang introduces long noncoding RNAs, or lncRNAs. As their name suggests, lncRNAs are not translated into proteins, and initially their functions were poorly understood. Chang’s group has developed technologies to better understand the function of lncRNAs. For example, his lab characterized the protein partners that interact with Xist, a canonical lncRNA that mediates X chromosome inactivation. They found that the protein Spen is necessary for X chromosome silencing. Interestingly, Spen has likely been co-opted by mammalian cells to inactivate the X chromosome via viral mimicry.

In his Part 3, Chang reminds us that every lncRNA gene has its own set of DNA regulatory elements, such as enhancers and promoters. These regulatory elements can confer functionality to lncRNA genes. Chang shares the research story of a mysterious lncRNA known as PVT1, which is frequently co-amplified with the proto-oncogene MYC in human cancers. His group found that PVT1 promoter activity is inversely correlated with MYC expression - when one is up, the other is down. Finally, Chang shows that the PVT1 and MYC promoters compete for four enhancers located within the PVT1 gene locus.

Speaker Biography:
Howard Chang is the Virginia and D. K. Ludwig Professor of Cancer Genomics and a professor of dermatology and genetics at Stanford University. He is an Investigator of the Howard Hughes Medical Institute. He studied biochemistry at Harvard University and completed a doctorate in biology at the Massachusetts Institute of Technology and medical degree at Harvard Medical School. The Chang lab pioneers new technologies for probing the function of the non-coding genome.

[ecesari]

One of the best quality lessons i've seen on youtube. I enjoyed, thank you! ^-^

[greghampikian]

I have assigned this to my graduate class, Viral/Human Coevolution. Thank you!

[mmartin]

Fascinating advances in imaging accessible DNA!

[DG-xgvg]

The female cell treats the male chromosome like a bunch of viral genes to inactivate the promoters. That's fascinating.

[salvadorhirth]

Thanks Dr. Howard Chang. I need to watch your video sometimes until I can understand all of it. I'd like to comment on my hypothesys for the cause of Huntington's disease: I believe that stop codons are formed when the carbon '5 in cytosines from CAG triplets are methilated and a subsequent deamination transforms C into T, creating the stop codon TAG. If my hypothesis is correct, I wonder if an existing drug like Decitabine could retard or prevent the onset of Huntington's. Perhaps stop codons are the cause of other neurodegenerative diseases, like the transformation of CGA codons into TGA codons in Parkingsons.
Also, if you have time let me know if a restriction enzyme specific for the palindromic region of +ss RNA viruses, like the Coronavirus, could cleave the viral RNA inside cells, provided its possible to get the restiction enzymes molecules inside the cytoplasm. Thanks again for your consideration!
Salvador

[TheDarim]

I wonder if these data on the mechanism of silencing of viral genes by human cells could somehow explain the individual differences (or maybe even sex-related differences) in human susceptibility to viral diseases....

[aysehaleguckr]

Thanks Dr. Howard Chang. This is very helpful video. I would like to ask you that is it possible for any drug not to target any lncrna? I am writing a project about targeting lncRNAs with drug for cancer cells. However I couldn't convince referees about targeting lncRNAs. Could you please give me some advice.

[numericalcode]

This essentially a very complex chemical computation

[johachinjoel]

Hopefully, you won't get bash by the Trans agenda for saying that men and women are biologically different. Thanks for the video.

[owoeyepaul]

That doesn't make it a lie that God made the woman different from the man. Of course, there has to be a mechanism for bringing about the difference in creatures meant to be equal in worth and usefulness, but complementary(not similar) in works(physiologically, psychologically, and such like) and form(anatomically).

To create is Divine. Why is the gorilla not as wise as man? God made some things inactive by one mechanism or the other in them, but made it active in man. We humans are to search out if we have the time.

The glory of God is to conceal a matter, but the honour of Kings is to reveal it, so the Bible says.

NO DOUBT, THERE'S NO WISE HUMAN; WE ALL LEARN ONLY A LITTLE OF THE MIGHTY WISDOM OF CREATION. SO WHY BE PROUD? GOD'S WORDS WE MUST OBEY.

[joeschmoe]

PLZ MORE EPIGENETICS!! MY APPETITE CANNOT BE SATIATED!!!