Two proteins that control nuclear DNA distribution also regulate development by altering gene expression

Jun 19, 2013
Cell biology: DNA directors discovered
In normal muscle cells (left), heterochromatin (blue) is localized at the edges of the nucleus. In cells lacking both LBR and LamA/C (right), heterochromatin is in the center of the nucleus. Credit: 2013 Irina Solovei, Ludwig Maximilians University Munich

Cell biologists believe that gene expression in eukaryotic cells is partly controlled by the uneven distribution of DNA in the nucleus. Colin Stewart and Audrey Wang at the A*STAR Institute of Medical Biology, Singapore, and their international co-workers, have identified two proteins that control this distribution of DNA. Their findings have important implications for disease and cellular development.

Heterochromatin is DNA that is tightly packed to prevent expression of its genes, and it is mainly tethered to the inside of the nucleus wall, also called the 'nuclear envelope'. Euchromatin is DNA that is loosely packed and ready for , and it is in the center of the nucleus.

Stewart and Wang discovered that DNA distribution depends on two proteins found in the : lamin B receptor (LBR) and lamin A/C (lamA/C). They discovered that neither of these proteins is expressed in a type of photoreceptor cell that naturally has a reversed distribution of heterochromatin and euchromatin. When the researchers removed both LBR and lamA/C from normal , they observed the same reversal, proving that the absence of these proteins is responsible for this DNA distribution.

According to Stewart, the involvement of LBR and lamA/C has important consequences. "Mutations in the lamin proteins cause a range of inherited diseases, including muscular dystrophy, enlargement of the heart, premature aging and diseases affecting and fat production," he explains. "These [conditions] are rare, but studying them may provide insights into more pressing diseases, such as cardiovascular disease, obesity and aging."

Looking at the roles of LBR and lamA/C in more detail, Stewart and Wang also found that the proteins are expressed at different times during embryonic development; LBR is expressed initially, but it is replaced over time by lamA/C. In , the two proteins also had opposite effects on the expression of muscle-specific genes: LBR silenced the genes, whereas lamA/C switched them on. The combination of differential expression and gene activation allows the two proteins to orchestrate cellular development.

The team's work answers some questions about the mechanisms and importance of uneven DNA distribution. Stewart notes, however, that there are now many more questions to investigate. "Is the disruption to heterochromatin a cause or consequence of diseases? What does this effect on chromatin structure mean for the stability of the genome? Does it increase susceptibility to other diseases, such as cancer?" he asks. "These are avenues that we will now pursue."

Explore further: DNA-altering enzyme is essential for blood cell development

More information: Solovei, I., Wang, A. S., Thanisch, K., Schmidt, C. S., Krebs, S. et al. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152, 584–598 (2013). www.cell.com/abstract/S0092-8674%2813%2900012-3

add to favorites email to friend print save as pdf

Related Stories

Programming cells: The importance of the envelope

Feb 01, 2013

In a project that began with the retinal cells of nocturnal animals and has led to fundamental insights into the organization of genomic DNA, researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich show how the nuclear ...

DNA-altering enzyme is essential for blood cell development

Jun 10, 2013

The expression of specific genes is partially dictated by the way the DNA is packed into chromatin, a tightly packed combination of DNA and proteins known as histones. HDAC3 is a chromatin-modifying enzyme that regulates ...

Do we owe our sense of smell to epigenetics?

Mar 05, 2013

(Phys.org) —Olfactory sensory neurons – nerve cells in the nose – directly sense molecules that convey scent, then send the signals to the brain. Biologists have long wondered how it's possible for ...

Clues point to cause of a rare fat-distribution disease

Mar 20, 2013

Studying a protein that gives structure to the nucleus of cells, Johns Hopkins researchers stumbled upon mutations associated with familial partial lipodystrophy (FPLD), a rare disease that disrupts normal patterns of fat ...

Recommended for you

For cells, internal stress leads to unique shapes

11 hours ago

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these ...

Adventurous bacteria

12 hours ago

To reproduce or to conquer the world? Surprisingly, bacteria also face this problem. Theoretical biophysicists at Ludwig-Maximilians-Universitaet (LMU) in Munich have now shown how these organisms should ...

Revealing camouflaged bacteria

14 hours ago

A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial pathogen Salmonella within the cells. The so cal ...

User comments : 0

More news stories

More vets turn to prosthetics to help legless pets

A 9-month-old boxer pup named Duncan barreled down a beach in Oregon, running full tilt on soft sand into YouTube history and showing more than 4 million viewers that he can revel in a good romp despite lacking ...

Revealing camouflaged bacteria

A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial pathogen Salmonella within the cells. The so cal ...

New clinical trial launched for advance lung cancer

Cancer Research UK is partnering with pharmaceutical companies AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer – marking a new era of research into personalised medicines ...