Working in harmony: New insights into how packages of DNA orchestrate development

February 15, 2018

SALT LAKE CITY - New research from Huntsman Cancer Institute (HCI) at the University of Utah (U of U) illuminates aspects of how an early embryo, the product of fertilization of a female egg cell by a male sperm cell, can give rise to all the many cell types of the adult animal. Researchers demonstrated that the hundreds of genes important for controlling embryonic development are all packaged in a unique manner in the early embryo - and even as far back as the paternal sperm - and that this packaging helps control how, when, and where different genes are expressed in the embryo. The findings, published today in the journal Cell, have significant implications for understanding how early development is orchestrated, and provides a mechanism for how parental environment might impact the expression of these genes in the offspring.

Brad Cairns, PhD, HCI senior director of basic science and professor and chair of Oncological Sciences at the U of U, and his colleagues, including postdoctoral fellow Patrick Murphy PhD, used zebrafish in this work, a model system that maintains significant similarities to human development. They demonstrated that DNA segments (genes) important for controlling development are packaged in physical structures that help turn 'on' and 'off' genes at different stages of development. These physical structures serve as platforms that help activate or poise these genes, as needed, for normal development. The researchers also identified the protein machines that place these physical structures into the genome, and the proteins that remove them, to ensure their proper placement and function. This work builds upon several prior studies from the Cairns lab that show that show how genes prepare themselves for different aspects of embryonic development.

"A key question in embryonic development is how the early embryo achieves the state of totipotency that it displays - that is ability to become any type of cell in the body. We reasoned that the central answer might be to package all the decision-making genes in a special physical state that helps identify and regulate them," explains Cairns.

Researchers have long sought to better understand whether and how genes from mom and dad might be packaged in a manner that influences expression and development in the embryo, and how those packaging states are maintained or reprogrammed during the development process. This study identifies that packaging - termed histone variant H2AFV - and provides a mechanism for inheriting gene packaging, and therefore has important implications for developmental potential and inheritance. Remarkably, although the initial packaging of genes in the paternal sperm differs somewhat from packaging in the maternal egg, the maternal packaging was shown to reprogram to the same packaging state of the paternal genome, thus harmonizing the packaging states from the parents in the early embryo to arrive at the same cellular development state.

The implications of this work include a possible mechanism for how environmental factors - for example, smoking - might influence inheritance of traits, by affecting how developmental genes are packaged. "These packaging states help to define whether and how genes are expressed in normal development. Such genes, if misregulated can lead to developmental disorders, and perhaps to predisposition for cancer," says Cairns. "By better understanding what happens in normal development, it opens up new possibilities for being able to identify the precursors to diseases like cancer, when cell development goes haywire."
-end-
The work was supported by the National Institutes of Health/National Cancer Institute P30 CA24014, National Institutes of Health T32HD007491, the Howard Hughes Medical Institute, and the Huntsman Cancer Foundation.

Huntsman Cancer Institute (HCI) at the University of Utah is the official cancer center of Utah. The cancer campus includes a state-of-the-art cancer specialty hospital as well as two buildings dedicated to cancer research. HCI treats patients with all forms of cancer and operates several clinics that focus on patients with a family history of cancer. As the only National Cancer Institute (NCI)-Designated Comprehensive Cancer Center in the Mountain West, HCI serves the largest geographic region in the country, drawing patients from Utah, Nevada, Idaho, Wyoming, and Montana. HCI scientists have identified more genes for inherited cancers than any other cancer center in the world, including genes responsible for hereditary breast, ovarian, colon, head, and neck cancers, along with melanoma. HCI manages the Utah Population Database - the largest genetic database in the world, with information on more than 9 million people linked to genealogies, health records, and vital statistics. The institute was founded by Jon M. and Karen Huntsman.

University of Utah

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.