Changes to the structure of the protein histone H3.3 may play a key role in silencing genes that regulate cancer cell growth, according to a study led by researchers from the Icahn School of Medicine at Mount Sinai and published online this month in the journal Nature Communications. According to the authors, this is the first study to identify this protein as a key regulator in cellular senescence, a process in which cells stop multiplying.
Cellular senescence has garnered significant scientific interest of late because it may be one key to prevent the initiation of cancer. However, little is known about this process and how genes that enable cells to divide and multiply (the cell cycle) are turned off. A growing body of evidence suggests that the process of cellular senescence is driven by changes in the protein complexes called chromatin in the nuclei of cells.
Using models of senescence, researchers found that histone variant H3.3, a protein that works closely with chromatin to package and regulate genetic material within cells, and in particular its clipped form, help to silence target genes that regulate the cell cycle.
Could the presence of this protein stop cells from dividing? Indeed using genome-wide transcriptional profiling, the researchers revealed that expression of clipped H3.3 silences genes that regulate the division and duplication of a cell.
"Cellular senescence creates a chromatin environment that represses cell multiplication, and thus cell or tumor growth, but how this happens molecularly is what we sought to discover," said lead investigator Emily Bernstein, PhD, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai. "What we found was that histone H3.3 and its clipped form, which lacks 21 amino acids of the histone tail and associated modifications, prevents normal cells from dividing. Clipped H3.3 may be a marker of cells that stop proliferating and has implications for cancer, in particular cancers like melanoma that have a senescence phase."
This research was supported by a grant from the National Cancer Institute, University of Cambridge, Cancer Research UK, Hutchinson Whampoa and the Human Frontier Science Program, funds from The Ellison Medical Foundation, and a Developmental Research Pilot Project Program at Mount Sinai.
About the Tisch Cancer Institute
The Tisch Cancer Institute (TCI) is a world-class translational cancer institute established in December 2007. TCI has recruited more than 30 acclaimed physicians and researchers specializing in basic research, clinical research, and population science; built outstanding programs in solid tumor oncology; enhanced existing robust programs in hematological malignancies; and advanced the study of cancer immunology and vaccine therapy. The completion of the Leon and Norma Hess Center for Science and Medicine in 2012 is enabling the recruitment of up to 20 additional cancer researchers on two full research floors, with 48,000 square feet of space dedicated to cancer research.
To learn more about clinical trials at Mount Sinai, visit http://icahn.mssm.edu/research/clinical-trials
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care.
The System includes approximately 6,600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.
For more information, visit http://www.mountsinai.org , or find Mount Sinai on Facebook, Twitter and YouTube.
Lucia Lee | EurekAlert!
Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology
Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
18.10.2017 | Materials Sciences
18.10.2017 | Physics and Astronomy
18.10.2017 | Physics and Astronomy