Nav: Home

Nuclear architecture: What organizes the genome in the nucleus?

June 06, 2019

Spatial separation of active from inactive fractions of the genome in the cell nucleus is crucial for gene expression control. A new study uncovers leading mechanisms of such separation and turns our picture of the nucleus upside down.

Eukaryotic chromosomes are built of chromatin, a complex of DNA and associated proteins. Depending on transcriptional activity and degree of compaction, two types of chromatin can be distinguished and these two types are spatially separated within the nucleus. The highly condensed fraction is made up of regions of chromatin that contain few genes and is transcriptionally inactive. It is called heterochromatin, and is located in the periphery of the nucleus, close to the nuclear membrane. Euchromatin, on the other hand, is enriched in genes and corresponds to the active fraction of the genome. It occupies the inner regions of the nucleus, is less densely packed, and therefore more accessible to the protein machineries required for gene expression. This general pattern of genome organization is found in virtually all eukaryotic cell types, but the mechanisms establishing the characteristic distribution remain poorly understood. Research carried out by a team led by Irina Solovei at Ludwig-Maximilians-Universitaet (LMU) in Munich's Biocenter, in cooperation with Job Dekker (University of Massachusetts Medical School) and physicists from the group of Leonid Mirny at MIT (Institute for Medical Engineering and Science) now suggests that the driving force in chromatin segregation is the inactive heterochromatin and that in the 'default' chromatin distribution of euchromatin and heterochromatin are reversed. The new findings appear in the leading journal Nature.

Many mechanisms have been proposed to explain how chromatin is segregated within the nucleus, however none of them were conclusive, largely, because it is difficult to analyze the interactions of the two chromatin types in the context of conventional nuclei with heterochromatin tethered to the nuclear membrane. "For our study, we therefore chose so called inverted cell nuclei," says Solovei. She and her Munich colleagues discovered these nuclei about 10 years ago in the retina of nocturnally active mammals, where they are restricted to the type of photoreceptor cells known as rods. In rods, the tightly condensed heterochromatin is packed in the interior of the nuclei, while the active euchromatin is localized directly under the nuclear membrane - a unique exception to the general rule. It turned out that the heterochromatin core of rod nuclei serves as a microlens condensing light and thus improving optical properties in the nocturnal retinas. Subsequent study from the same group disclosed the mechanism of inversion by revealing that these atypical nuclei lack two protein complexes that normally link the heterochromatin to the inner surface of the nuclear membrane, the nuclear lamina.

Using data obtained by a combination of modern microscopy and molecular biology techniques, the researchers have now generated polymer models of the individual chromosomes and of entire nuclei. By simulating the behavior of these polymers under different conditions, they were able to investigate the role of interactions within and between the two chromatin fractions and the nuclear lamina. These studies showed that interactions between heterochromatic regions alone are sufficient for chromatin segregation, whereas interactions within euchromatin are dispensable for this process. "Our results indicate that the inverted nucleus conceptually represents the default nuclear architecture," says Mirny; "while interactions of heterochromatin with the nuclear lamina are essential for building the conventional architecture". "In this respect," says Solovei, "it is intriguing to ask why the majority of eukaryotes have conventional nuclei, and what the functional relevance of heterochromatin positioning at the nuclear periphery might be."

Ludwig-Maximilians-Universität München

Related Genome Articles:

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.
Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.
Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.
A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.
How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.
Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.
Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.
Why do we need one pair of genome?
Scientists have unraveled how the cell replication process destabilizes when it has more, or less, than a pair of chromosome sets, each of which is called a genome -- a major step toward understanding chromosome instability in cancer cells.
A new genome for regeneration research
The first complete genome assembly of planarian flatworm reveals a treasure trove on the function and evolution of genes.
Decoding the Axolotl genome
The sequencing of the largest genome to date lays the foundation for novel insights into tissue regeneration.
More Genome News and Genome Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 2: Every Day is Ignaz Semmelweis Day
It began with a tweet: "EVERY DAY IS IGNAZ SEMMELWEIS DAY." Carl Zimmer – tweet author, acclaimed science writer and friend of the show – tells the story of a mysterious, deadly illness that struck 19th century Vienna, and the ill-fated hero who uncovered its cure ... and gave us our best weapon (so far) against the current global pandemic. This episode was reported and produced with help from Bethel Habte and Latif Nasser. Support Radiolab today at