Doe Science news source
The DOE Science News Source is a Newswise initiative to promote research news from the Office of Science of the DOE to the public and news media.
  • 2017-06-21 13:00:29
  • Article ID: 676793

Researchers Find New Mechanism for Genome Regulation

Berkeley Lab study could have implications for improving gene therapy

  • Credit: Amy Strom/Berkeley Lab

    Liquid-like fusion of heterochromatin protein 1a droplets in the embryo of a fruit fly.

  • Credit: Amy Strom/Berkeley Lab

    Shown is purified heterochromatin protein 1a forming liquid droplets in an aqueous solution. On the right side, two drops fuse together over time.

  • Credit: Amy Strom/Berkeley Lab

    Mouse fibroblast cells expressing HP1alpha, the human version of heterochromatin protein 1a. A technique that highlights edges between two liquid phases reveals the liquid droplets in the nucleus.

The same mechanisms that quickly separate mixtures of oil and water are at play when controlling the organization in an unusual part of our DNA called heterochromatin, according to a new study by researchers at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab).

Researchers studying genome and cell biology provide evidence that heterochromatin organizes large parts of the genome into specific regions of the nucleus using liquid-liquid phase separation, a mechanism well known in physics but whose importance for biology has only recently been revealed. 

They present their findings June 21 in the journal Nature, addressing a long-standing question about how DNA functions are organized in space and time, including how genes are regulated to be silenced or expressed.

“The importance of DNA sequences in health and disease has been clear for decades, but we only recently have come to realize that the organization of sections of DNA into different physical domains or compartments inside the nucleus is critical to promote distinct genome functions,” said study corresponding author, Gary Karpen, senior scientist at Berkeley Lab's Biological Systems and Engineering Division.

The long stretches of DNA in heterochromatin contain sequences that, for the most part, need to be silenced for cells to work properly. Scientists once thought that compaction of the DNA was the primary mechanism for controlling which enzymes and molecules gain access to the sequences. It was reasoned that the more tightly wound the strands, the harder it would be to get to the genetic material inside.

That mechanism has been questioned in recent years by the discovery that some large protein complexes could get inside the heterochromatin domain, while smaller proteins can remain shut out.

In this new study of early Drosophila embryos, the researchers observed two non-mixing liquids in the cell nucleus: one that contained expressed genes, and one that contained silenced heterochromatin. They found that heterochromatic droplets fused together just like two drops of oil surrounded by water.

In lab experiments, researchers purified heterochromatin protein 1a (HP1a), a main component of heterochromatin, and saw that this single component was able to recreate what they saw in the nucleus by forming liquid droplets.

"We are excited about these findings because they explain a mystery that's existed in the field for a decade," said study lead author Amy Strom, a graduate student in Karpen's lab. "That is, if compaction controls access to silenced sequences, how are other large proteins still able to get in? Chromatin organization by phase separation means that proteins are targeted to one liquid or the other based not on size, but on other physical traits, like charge, flexibility, and interaction partners."

The Berkeley Lab study, which used fruit fly and mouse cells, will be published alongside a companion paper in Nature led by UC San Francisco researchers, who showed that the human version of the HP1a protein has the same liquid droplet properties, suggesting that similar principles hold for human heterochromatin.

Interestingly, this type of liquid-liquid phase separation is very sensitive to changes in temperature, protein concentration, and pH levels.

"It's an elegant way for the cell to be able to manipulate gene expression of many sequences at once," said Strom.

Other cellular structures, including some involved in disease, are also organized by phase separation.

"Problems with phase separation have been linked to diseases such as dementia and certain neurodegenerative disorders," said Karpen.

He noted that as we age, biological molecules lose their liquid state and become more solid, accumulating damage along the way. Karpen pointed to diseases like Alzheimer's and Huntington's, in which proteins misfold and aggregate, becoming less liquid and more solid over time.

"If we can better understand what causes aggregation, and how to keep things more liquid, we might have a chance to combat these types of disease," Strom added.

The work is a big step forward for understanding how DNA functions, but could also help researchers improve their ability to manipulate genes.

“Gene therapy, or any treatment that relies on tight regulation of gene expression, could be improved by precisely targeting molecules to the right place in the nucleus,” says Karpen. “It is very difficult to target genes located in heterochromatin, but this understanding of the properties linked to phase separation and liquid behaviors could help change that and open up a third of the genome that we couldn’t get to before.” 

This includes targeting gene-editing technologies like CRISPR, which has recently opened up new doors for precise genome manipulation and gene therapy.

Karpen and Strom have joint appointments at UC Berkeley's Department of Molecular and Cell Biology. Other study co-authors include Mustafa Mir and Xavier Darzacq at UC Berkeley, and Alexander Emelyanov and Dmitry Fyodorov at the Albert Einstein College of Medicine in New York. 

The National Institutes of Health and the California Institute for Regenerative Medicine helped support this work.

###

Lawrence Berkeley National Laboratory addresses the world’s most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab’s scientific expertise has been recognized with 13 Nobel Prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy’s Office of Science. For more, visit www.lbl.gov.

DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

X
X
X
  • Filters

  • × Clear Filters

Coupling Experiments to Theory to Build a Better Battery

A Berkeley Lab-led team of researchers has reported that a new lithium-sulfur battery component allows a doubling in capacity compared to a conventional lithium-sulfur battery, even after more than 100 charge cycles.

DRIFTing to Fast, Precise Data

Non-destructive technique identifies key variations in Alaskan soils, quickly providing insights into carbon levels.

A Shortcut to Modeling Sickle Cell Disease

Using Oak Ridge National Laboratory's Titan supercomputer, a team led by Brown University's George Karniadakis devised a multiscale model of sickle cell disease that captures what happens inside a red blood cell affected by the disease.

Remotely Predicting Leaf Age in Tropical Forests

New approach offers data across species, sites, and canopies, providing insights into carbon uptake by forests.

Conservation Mind Game

A new study led by Kathryn Caldwell, an assistant professor of psychology at Ithaca College, demonstrates that homeowners can be encouraged to make changes to their energy use with a simple education plan and some helpful tricks from the world of social psychology.

X-Rays Reveal 'Handedness' in Swirling Electric Vortices

Scientists used spiraling X-rays at Berkeley Lab to observe, for the first time, a property that gives left- or right-handedness to swirling electric patterns - dubbed polar vortices - in a layered material called a superlattice.

Breaking Bad Metals with Neutrons

By combining the latest developments in neutron scattering and theory, researchers are close to predicting phenomena like superconductivity and magnetism in strongly correlated electron systems. It is likely that the next advances in superconductivity and magnetism will come from such systems, but they might also be used in completely new ways such as quantum computing.

ORNL Researchers Use Titan to Accelerate Design, Training of Deep Learning Networks

For deep learning to be effective, existing neural networks to be modified, or novel networks designed and then "trained" so that they know precisely what to look for and can produce valid results. This is a time-consuming and difficult task, but one that a team of ORNL researchers recently demonstrated can be dramatically expedited with a capable computing system.

Dark Energy Survey Publicly Releases First Three Years of Data

At a special session held during the American Astronomical Society meeting in Washington, D.C., scientists on the Dark Energy Survey (DES) announced today the public release of their first three years of data. This first major release of data from the Survey includes information on about 400 million astronomical objects, including distant galaxies billions of light-years away as well as stars in our own galaxy.

Ingredients for Life Revealed in Meteorites That Fell to Earth

A detailed study of blue salt crystals found in two meteorites that crashed to Earth - which included X-ray experiments at Berkeley Lab - found that they contain both liquid water and a mix of complex organic compounds including hydrocarbons and amino acids.


  • Filters

  • × Clear Filters

Superconducting X-Ray Laser Takes Shape in Silicon Valley

An area known for high-tech gadgets and innovation will soon be home to an advanced superconducting X-ray laser that stretches 3 miles in length, built by a collaboration of national laboratories. On January 19, the first section of the machine's new accelerator arrived by truck at SLAC National Accelerator Laboratory in Menlo Park after a cross-country journey that began in Batavia, Illinois, at Fermi National Accelerator Laboratory.

Kelsey Stoerzinger Earns Young Investigator Lectureship

Kelsey Stoerzinger, Pauling Fellow at Pacific Northwest National Laboratory, is one of the 2018 Caltech Young Investigator Lecturers in Engineering and Applied Physics.

North Dakota State University Joins Two National Distributed Computing Groups

The NDSU Center for Computationally Assisted Science and Technology (CCAST) joins OSG (Open Science Grid) and XSEDE (Extreme Science and Engineering Discovery Environment).

DOE Announces Funding for New HPC4Manufacturing Industry Projects

The Department of Energy's Advanced Manufacturing Office (AMO) today announced the funding of $1.87 million for seven new industry projects under an ongoing initiative designed to utilize DOE's high-performance computing (HPC) resources and expertise to advance U.S. manufacturing and clean energy technologies.

DOE Announces First Awardees for New HPC4Materials for Severe Environments Program

The Department of Energy's Office of Fossil Energy (FE) today announced the funding of $450,000 for the first two private-public partnerships under a brand-new initiative aimed at discovering, designing and scaling up production of novel materials for severe environments.

Two Argonne Scientists Recognized for a Decade of Breakthroughs

Two scientists with the U.S. Department of Energy's (DOE) Argonne National Laboratory have been named to the Web of Science's Highly Cited List of 2017, ranking in the top 1 percent of their peers by citations and subject area. Materials Scientist Khalil Amine and Energy and Environmental Policy Scientist David Streets say they are thrilled to see their work -- and the laboratory -- recognized in such a way.

Argonne Welcomes Department of Energy Secretary Perry

U.S. Department of Energy Secretary Rick Perry visited Argonne National Laboratory yesterday, getting a first-hand view of the multifaceted and interdisciplinary research program laboratory of the Department.

Argonne names John Quintana Deputy Laboratory Director for Operations and COO

John Quintana has been named Deputy Laboratory Director for Operations and Chief Operations Officer (COO) of the U.S. Department of Energy's (DOE) Argonne National Laboratory.

Developing Next-Generation Sensing Technologies

Recently, the Advanced Research Projects Agency-Energy (ARPA-E) announced $20 million in funding for 15 projects that will develop a new class of sensor systems to enable significant energy savings via reduced demand for heating and cooling in residential and commercial buildings.

Supporting the Development of Offshore Wind Power Plants

Offshore wind is becoming a reality in the United States, especially in the northeast states. To support this development, the Center for Future Energy System (CFES) at Rensselaer Polytechnic Institute will present a webinar titled "Turbine and Transmission System Technologies for Offshore Wind (OSW) Power Plants." The program will be held on Wednesday, Dec. 20, from 2 to 4 p.m. Advance registration is required.


  • Filters

  • × Clear Filters

Exploring Past, Present, and Future Water Availability Regionally, Globally

New open-source software simulates river and runoff resources.

Arctic Photosynthetic Capacity and Carbon Dioxide Assimilation Underestimated by Terrestrial Biosphere Models

New measurements offer data vital to projecting plant response to environmental changes.

DRIFTing to Fast, Precise Data

Non-destructive technique identifies key variations in Alaskan soils, quickly providing insights into carbon levels.

Superconducting Tokamaks Are Standing Tall

Plasma physicists significantly improve the vertical stability of a Korean fusion device.

Graphene Flexes Its Muscle

Crumpling reduces rigidity in an otherwise stiff material, making it less prone to catastrophic failure.

Remotely Predicting Leaf Age in Tropical Forests

New approach offers data across species, sites, and canopies, providing insights into carbon uptake by forests.

What's the Noise Eating Quantum Bits?

The magnetic noise caused by adsorbed oxygen molecules is "eating at" the phase stability of quantum bits, mitigating the noise is vital for future quantum computers.

Rewritable Wires Could Mean No More Obsolete Circuitry

An electric field switches the conductivity on and off in atomic-scale channels, which could allow for upgrades at will.

Filtering Water Better than Nature

Water passes through human-made straws faster than the "gold standard" protein, allowing us to filter seawater.

Machine Learning Provides a Bridge to the Texture of the Quantum World

Machine learning and neural networks are the foundation of artificial intelligence and image recognition, but now they offer a bridge to see and recognize exotic insulating phases in quantum materials.


Spotlight

Wednesday January 17, 2018, 12:05 PM

Photographer Adam Nadel Selected as Fermilab's New Artist-in-Residence for 2018

Fermi National Accelerator Laboratory (Fermilab)

Wednesday January 17, 2018, 12:05 PM

Fermilab Computing Partners with Argonne, Local Schools for Hour of Code

Fermi National Accelerator Laboratory (Fermilab)

Wednesday December 20, 2017, 01:05 PM

Q&A: Sam Webb Teaches X-Ray Science from a Remote Classroom

SLAC National Accelerator Laboratory

Monday December 18, 2017, 01:05 PM

The Future of Today's Electric Power Systems

Rensselaer Polytechnic Institute (RPI)

Monday December 18, 2017, 12:05 PM

Supporting the Development of Offshore Wind Power Plants

Rensselaer Polytechnic Institute (RPI)

Tuesday October 03, 2017, 01:05 PM

Stairway to Science

Argonne National Laboratory

Thursday September 28, 2017, 12:05 PM

After-School Energy Rush

Argonne National Laboratory

Thursday September 28, 2017, 10:05 AM

Bringing Diversity Into Computational Science Through Student Outreach

Brookhaven National Laboratory

Thursday September 21, 2017, 03:05 PM

From Science to Finance: SLAC Summer Interns Forge New Paths in STEM

SLAC National Accelerator Laboratory

Thursday September 07, 2017, 02:05 PM

Students Discuss 'Cosmic Opportunities' at 45th Annual SLAC Summer Institute

SLAC National Accelerator Laboratory

Thursday August 31, 2017, 05:05 PM

Binghamton University Opens $70 Million Smart Energy Building

Binghamton University, State University of New York

Wednesday August 23, 2017, 05:05 PM

Widening Horizons for High Schoolers with Code

Argonne National Laboratory

Saturday May 20, 2017, 12:05 PM

Rensselaer Polytechnic Institute Graduates Urged to Embrace Change at 211th Commencement

Rensselaer Polytechnic Institute (RPI)

Monday May 15, 2017, 01:05 PM

ORNL, University of Tennessee Launch New Doctoral Program in Data Science

Oak Ridge National Laboratory

Friday April 07, 2017, 11:05 AM

Champions in Science: Profile of Jonathan Kirzner

Department of Energy, Office of Science

Wednesday April 05, 2017, 12:05 PM

High-Schooler Solves College-Level Security Puzzle From Argonne, Sparks Interest in Career

Argonne National Laboratory

Tuesday March 28, 2017, 12:05 PM

Champions in Science: Profile of Jenica Jacobi

Department of Energy, Office of Science

Friday March 24, 2017, 10:40 AM

Great Neck South High School Wins Regional Science Bowl at Brookhaven Lab

Brookhaven National Laboratory

Wednesday February 15, 2017, 04:05 PM

Middle Schoolers Test Their Knowledge at Science Bowl Competition

Argonne National Laboratory

Friday January 27, 2017, 04:00 PM

Haslam Visits ORNL to Highlight State's Role in Discovering Tennessine

Oak Ridge National Laboratory

Tuesday November 08, 2016, 12:05 PM

Internship Program Helps Foster Development of Future Nuclear Scientists

Oak Ridge National Laboratory

Friday May 13, 2016, 04:05 PM

More Than 12,000 Explore Jefferson Lab During April 30 Open House

Thomas Jefferson National Accelerator Facility

Monday April 25, 2016, 05:05 PM

Giving Back to National Science Bowl

Ames Laboratory

Friday March 25, 2016, 12:05 PM

NMSU Undergrad Tackles 3D Particle Scattering Animations After Receiving JSA Research Assistantship

Thomas Jefferson National Accelerator Facility

Tuesday February 02, 2016, 10:05 AM

Shannon Greco: A Self-Described "STEM Education Zealot"

Princeton Plasma Physics Laboratory

Monday November 16, 2015, 04:05 PM

Rare Earths for Life: An 85th Birthday Visit with Mr. Rare Earth

Ames Laboratory

Tuesday October 20, 2015, 01:05 PM

Meet Robert Palomino: 'Give Everything a Shot!'

Brookhaven National Laboratory

Tuesday April 22, 2014, 11:30 AM

University of Utah Makes Solar Accessible

University of Utah

Wednesday March 06, 2013, 03:40 PM

Student Innovator at Rensselaer Polytechnic Institute Seeks Brighter, Smarter, and More Efficient LEDs

Rensselaer Polytechnic Institute (RPI)

Friday November 16, 2012, 10:00 AM

Texas Tech Energy Commerce Students, Community Light up Tent City

Texas Tech University

Wednesday November 23, 2011, 10:45 AM

Don't Get 'Frosted' Over Heating Your Home This Winter

Temple University

Wednesday July 06, 2011, 06:00 PM

New Research Center To Tackle Critical Challenges Related to Aircraft Design, Wind Energy, Smart Buildings

Rensselaer Polytechnic Institute (RPI)

Friday April 22, 2011, 09:00 AM

First Polymer Solar-Thermal Device Heats Home, Saves Money

Wake Forest University

Friday April 15, 2011, 12:25 PM

Like Superman, American University Will Get Its Energy from the Sun

American University

Thursday February 10, 2011, 05:00 PM

ARRA Grant to Help Fund Seminary Building Green Roof

University of Chicago

Tuesday December 07, 2010, 05:00 PM

UC San Diego Installing 2.8 Megawatt Fuel Cell to Anchor Energy Innovation Park

University of California San Diego

Monday November 01, 2010, 12:50 PM

Rensselaer Smart Lighting Engineering Research Center Announces First Deployment of New Technology on Campus

Rensselaer Polytechnic Institute (RPI)

Friday September 10, 2010, 12:40 PM

Ithaca College Will Host Regional Clean Energy Summit

Ithaca College

Tuesday July 27, 2010, 10:30 AM

Texas Governor Announces $8.4 Million Award to Create Renewable Energy Institute

Texas Tech University

Friday May 07, 2010, 04:20 PM

Creighton University to Offer New Alternative Energy Program

Creighton University

Wednesday May 05, 2010, 09:30 AM

National Engineering Program Seeks Subject Matter Experts in Energy

JETS Junior Engineering Technical Society

Wednesday April 21, 2010, 12:30 PM

Students Using Solar Power To Create Sustainable Solutions for Haiti, Peru

Rensselaer Polytechnic Institute (RPI)

Wednesday March 03, 2010, 07:00 PM

Helping Hydrogen: Student Inventor Tackles Challenge of Hydrogen Storage

Rensselaer Polytechnic Institute (RPI)

Thursday February 04, 2010, 02:00 PM

Turning Exercise into Electricity

Furman University

Thursday November 12, 2009, 12:45 PM

Campus Leaders Showing the Way to a Sustainable, Clean Energy Future

National Wildlife Federation (NWF)

Tuesday November 03, 2009, 04:20 PM

Furman University Receives $2.5 Million DOE Grant for Geothermal Project

Furman University

Thursday September 17, 2009, 02:45 PM

Could Sorghum Become a Significant Alternative Fuel Source?

Salisbury University

Wednesday September 16, 2009, 11:15 AM

Students Navigating the Hudson River With Hydrogen Fuel Cells

Rensselaer Polytechnic Institute (RPI)





Showing results

0-4 Of 2215