Scientists find a protein that controls DNA organization during sperm development

May 13, 2014, Cold Spring Harbor Laboratory
Researchers have discovered that a protein, called Chd5, plays an important role in male fertility. On the left is a sperm cell from a mouse that has two normal copies of the Chd5 gene. The sperm is healthy and the mouse is fertile. In the absence of Chd5, mice are infertile and their sperm cells are misshapen (three examples on the right). The researchers discovered that loss of Chd5 disrupts DNA packaging which causes infertility. Credit: Alea Mills, Cold Spring Harbor Laboratory

Infertility is generally thought of as a woman's problem. In fact, more than 3 million men across America also experience it. Today, researchers from Cold Spring Harbor Laboratory (CSHL) describe a key event during sperm development that is essential for male fertility. A team led by CSHL Professor Alea Mills explains how a protein controls DNA packaging to protect a man's genetic information.

The sperm is a simple delivery vehicle for a man's . The highly specialized cell is little more than a DNA bundle powered by molecular motors. As such, it is necessarily tiny: from head to tail a sperm cell is only about 50 micrometers long (1/500th of an inch), invisible to the naked eye. An egg is 30 times larger. The sperm's small size has its benefits – less bulk to carry while searching for an egg – but it also presents significant challenges. A man's genetic material must be very tightly packaged to fit within a minuscule space.

This organizational problem is not unique to sperm. Every cell in our body contains a full human genome, which spans nearly two meters (6 feet) if unfurled. To contain this massive length of DNA, cells tightly compress our genetic information. In every cell nucleus, DNA is wrapped like thread around protein spools, called histones. The thread can be easily unwound at any time to allow access to the genetic information. In sperm, the packaging problem is much more acute, as its DNA is even more condensed. The spool-like histones are replaced with tiny proteins called protamines. This repackaging process, called chromatin remodeling, is absolutely essential for .

In work published today in Nature Communications, Mills and her team identify a protein, called Chd5, as a key regulator of chromatin remodeling during sperm development. Mills and Wangzhi Li, PhD, lead author on the study, removed both copies of the Chd5 gene from male mice. They discovered that these males had severe fertility defects, ranging from low sperm counts to decreased . The defective sperm failed to fertilize eggs when in vitro fertilization (IVF) was performed.

Mills has been interested in Chd5 since the time that her team first discovered it in 2007 as a potent tumor suppressor, one that can stop cells from becoming cancerous. "We know this ability has something to do with chromatin remodeling—that when defective, causes normal cells to transform into tumors," says Mills. "But the most dramatic chromatin reorganization occurs when specialized cells carrying our genetic blueprint develop into . It makes sense that Chd5 would be functioning there, too."

This, indeed, is what Mills and her team found. When Chd5 is missing, chromatin remodeling is disrupted. Histones are not efficiently replaced with protamines to repackage DNA, resulting in a more uneven, less condensed genome.

This change in DNA packaging has dramatic effects on the DNA itself. In the absence of Chd5, the double helix becomes damaged, breaking at multiple points throughout the genome. "So in addition to infertility, loss of Chd5 may put future generations – the rare embryos that do get fertilized with defective sperm – at risk for disease," says Mills. "Chd5 may protect a person from medical conditions related to DNA damage and spontaneous mutations, like cancer and autism."

The team is actively studying the role of Chd5 in human fertility. They analyzed Chd5 levels using data from testes biopsies obtained from men with fertility defects. "We found that men with more severe defects had the lowest levels of Chd5," says Mills. "While it is only a correlation at this point, we are eager to understand fully how Chd5 affects development in humans."

Explore further: Team finds mechanism of one of the most powerful tumor-suppressor proteins, Chd5

More information: "Chd5 orchestrates chromatin remodeling during sperm development" appears online in Nature Communications on May 13, 2014.

Related Stories

Team finds mechanism of one of the most powerful tumor-suppressor proteins, Chd5

January 10, 2013
A team of cancer researchers at Cold Spring Harbor Laboratory (CSHL) has solved the mystery of how one of the most powerful of the body's natural tumor-suppressing proteins, called Chd5, exerts its beneficial effects.

First vital step in fertilization between sperm and egg discovered

April 16, 2014
Researchers at the Wellcome Trust Sanger Institute have discovered interacting proteins on the surface of the sperm and the egg essential to begin mammalian life. These proteins, which allow the sperm and egg to recognize ...

How developing sperm stick to the right path

March 24, 2014
The process of producing high-quality, fertile sperm requires many steps. A study in The Journal of Cell Biology shows how the transcription factor p73 promotes this process by regulating the adhesions between developing ...

Lack of seipin in testes could cause male infertility

April 29, 2014
(Medical Xpress)—Jiahao Sha and his colleagues at Nanjing University in China studied humans and mice with genetic abnormalities that prevent them from producing a protein called seipin. Lack of seipin causes body fat to ...

Recommended for you

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.