Author response: Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally
Year: 2015
Type: peer-review
Abstract: During fertilization, an egg cell and a sperm cell combine to make a cell called a zygote that then divides many times to form an embryo. Many of the characteristics of the embryo are determined by the genes it inherits from its parents. However, not all of these genes should be “expressed” to produce their products all of the time. One way of controlling gene expression is to add a chemical group called a methyl tag to the DNA near the gene, or to one of the histone proteins that DNA wraps around. Soon after fertilization, a process called reprogramming occurs that begins with the removal of most of the methyl tags a zygote inherited from the egg and sperm cells. The zygote’s DNA is then newly methylated to activate a new pattern of gene expression. In mammals, some genes escape this reprogramming; these “imprinted” genes retain the methylation patterns inherited from the parents. Reprogramming is assisted by “maternal factors” that are inherited from the egg cell. Once reprogramming is completed, the maternal factors are destroyed as part of a process called the maternal-to-zygotic transition. A maternal factor called KDM1A can remove specific methyl tags from certain histone proteins, but how this affects the zygote is not well understood. Now, Wasson et al. (and independently Ancelin et al.) have investigated the role that KDM1A plays in mouse development. Wasson et al. genetically engineered mouse egg cells to contain little or no KDM1A. Zygotes created from egg cells that completely lack KDM1A die before or shortly after they have divided for the first time and fail to undergo the maternal-to-zygotic transition. Other egg cells that contain low levels of KDM1A can give rise to baby mice. However, many of these mice die soon after birth, and those that grow to adulthood behave in abnormal ways; for example, they display excessive chewing and digging. These disorders are linked to the disruption of DNA methylation at imprinted genes. The next challenge will be to further investigate the mechanisms by which defects in maternally deposited KDM1A exert their long-range effects on imprinted genes and altered behaviour. This is particularly important because of the recent discovery of three patients with birth defects that are linked to genetic variants in KDM1A.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2989541889