May 17, 2016

Dr. Krawetz team publishes study on how nuclease footprints in sperm project chromatin regulatory events

Packaged in an almost crystalline form, sperm DNA holds the father's genetic memory. "Nuclease Footprints in Sperm Project Past and Future Chromatin Regulatory Events" by the Wayne State University Research team of Graham Johnson, of the WSU Center for Molecular Medicine and Genetics; Meritxell Jodar, Ph.D., post-doctoral fellow with the Department of Obstetrics and Gynecology; and Roger Pique-Regi, Ph.D., assistant professor of Obstetrics and Gynecology, and of the WSU Center for Molecular Medicine and Genetics; and Stephen Krawetz, Ph.D., associate director of the C.S. Mott Center for Human Growth and Development, and the Charlotte B. Failing Professor of Fetal Therapy and Diagnosis in the WSU Department of Obstetrics and Gynecology, published in Nature's Scientific Reports, examines how this precious male cargo is packaged for delivery and future use.

Interestingly, even though humans, mice and bulls use the same set of proteins to package the DNA, they generate different solutions, yet it resolves in a tightly compacted but ordered structure analogous to preparing a suitcase for travel. The underlying difference appears to be how their respective DNA is packaged in anticipation of activation and very early development.

The most important genes for early organismal development, like essential items in a suitcase, may need faster access that may be different for different types of travel. In mice, this development program is very accelerated, taking a few weeks to birth, and is achieved in part by the Ctcf protein by interacting and organizing mouse sperm's DNA. The researchers show that these interactions can be visualized as footprints that etch a trail onto the genome that is carried to fertilization.

While human males use the same machinery when packaging the genome, Ctcf's association with human or bovine sperm genomes leaves no tracks. This striking difference between mouse and higher order mammals may explain evolutionary differences in the genome packaging and its impact in preparation for early activation and accelerated development in mouse. The authors suggest that the Ctcf-DNA footprints are preserved in mouse sperm to aid in this process.