FEB 09, 2020 6:17 PM PST

Learning More About X Chromosome Inactivation

WRITTEN BY: Carmen Leitch

Female mammals carry two X chromosomes, while male mammals carry an X and a Y chromosome. The X chromosome carries a thousand genes, so in females, one of the X chromosomes must be silenced to avoid serious consequences; when the genes on one of the X chromosomes are not shut off, it can cause death in embryos. Researchers have now found that a protein called SPEN is crucial for the inactivation of an X chromosome, and have learned how it silences X chromosome genes. The work has been reported in Nature.

A molecule called Xist, which is a long non-coding RNA, was known to initiate the silencing of genes on the X chromosome. "The exact molecular mechanisms by which Xist mediates gene silencing have been a mystery for decades," said European Molecular Biology Laboratory (EMBL) in Heidelberg and Institut Curie graduate student François Dossin.

In this work, Dossin and researchers in the group of Edith Heard, Director General of EMBL, reduced the level of SPEN in embryonic stem cells. When they did that, it stopped X-inactivation from happening. The scientists also identified the location on the X chromosome where SPEN binds and exerts its effect.

When Xist is produced, it moves to the X chromosome where SPEN is bound. There, it links to SPEN, accumulating on the X chromosome. SPEN can also influence the genomic regions that regulate the expression of active genes. When gene silencing has occurred, SPEN can detach from the chromosome, and the genes remain permanently silenced for the lifetime of a cell.

"We dissected SPEN's role during X chromosome inactivation using a wide array of classical and cutting-edge approaches," said Dossin.

The researchers showed that one particular part of SPEN, which is called SPOC, takes the lead in silencing genes by interfering with the transcription of DNA into RNA. It also interacts with various proteins that function in the synthesis of RNA, and plays a part in the remodeling and modification of chromatin (a complex of DNA and the proteins that package it).

More work will be necessary to fully understand all of the details of X chromosome inactivation.

"We found that SPEN interacts with several pathways linked to gene silencing. Given that SPEN accounts for nearly all the silencing during X-inactivation, the next question to address is how much each of those pathways contributes to gene silencing," explained Edith Heard, Director General of EMBL.

Sources: Phys.org via EMBL, Nature

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
NOV 27, 2020
Cell & Molecular Biology
UVC Rays May be a Bigger Cancer Risk Than Known
NOV 27, 2020
UVC Rays May be a Bigger Cancer Risk Than Known
The sun emits different kinds of light and rays including visible and ultraviolet (UV) and infrared. Some of those forms ...
DEC 03, 2020
Space & Astronomy
Health Issues from Spaceflight Caused by Mitochondria
DEC 03, 2020
Health Issues from Spaceflight Caused by Mitochondria
Spending an extended time in space is known to impact various aspects of health, from muscle and bone regeneration to th ...
DEC 06, 2020
Cell & Molecular Biology
Free Radicals May Actually be Good for the Brain
DEC 06, 2020
Free Radicals May Actually be Good for the Brain
Reactive oxygen species (ROS) are a type of highly reactive molecule that is thought to be damaging to cellular structur ...
DEC 13, 2020
Cell & Molecular Biology
The Immune Response to Infection and Vaccination Depends on Previous Infections
DEC 13, 2020
The Immune Response to Infection and Vaccination Depends on Previous Infections
After we are exposed to a pathogen or in the case of vaccines, a portion of a pathogen, our body mounts an immune respon ...
DEC 28, 2020
Cancer
Revealing a Critical Protein Involved in the Pentose Phosphate Pathway in Cancer
DEC 28, 2020
Revealing a Critical Protein Involved in the Pentose Phosphate Pathway in Cancer
The metabolism of cancer has interested scientists in recent decades. Many cancers conduct "normal" metabolism ...
JAN 22, 2021
Genetics & Genomics
Developmental Processes Are Active in Diseased Skin Cells
JAN 22, 2021
Developmental Processes Are Active in Diseased Skin Cells
Many different types of cells make up the human body, and the Human Cell Atlas is an initiative that has been aiming to ...
Loading Comments...