Gene repression might be sex-specific

Researchers have proven for the primary time that embryonic cells destined to develop into both egg or sperm depend on totally different strategies of repressive gene regulation.

The analysis was carried out on the Medical Research Council (MRC) London Institute of Medical Sciences (LMS).

For a gene to be expressed by a cell, the DNA that codes for it must be open and accessible to particular proteins. This means how compacted the DNA is has a direct impact on whether or not a gene might be energetic or not.

Methylation, a kind of chemical modification, is a type of epigenetic management cells use to silence gene expression. It does this by way of rising native DNA compaction. The methylation can happen:

• on to the DNA itself, by way of methylation of cytosine (one of many constructing blocks of DNA)
• on the histone proteins DNA is wrapped round contained in the cell nucleus.

During growth, primordial germ cells (PGCs, the embryonic precursors of gametes) lose virtually all DNA methylation earlier than they differentiate into both egg or sperm. This has left scientists questioning how these early germ cells regulate their gene expression, specifically what mechanisms they use to silence genes that shouldn’t be energetic.

Global DNA demethylation

To reply this, the MRC LMS Reprogramming and Chromatin analysis group, led by Professor Petra Hajkova, analyzed modes of gene repression happening in PGCs after that they had undergone international DNA demethylation. The workforce discovered that these germ cells use various repressive epigenetic methods and crucially, these methods are employed in another way in female and male germ cells.

Results counsel that methylation of K27 on histone-3 compensates for the lack of DNA methylation in PCGs and that it does this in a sex-specific method. Female germ cells critically depend on this method whereas the male germ cells additionally make the most of methylation of K9 on histone-3.

To discover this additional in a physiological context, the group analyzed a mouse mannequin the place the gene required for K27 methylation, Ezh2 had been eliminated. The group noticed that with out Ezh2, feminine germ cells expressed genes in an uncontrolled method, didn’t differentiate and subsequently died.

Interestingly, male PCGs weren’t affected. This helps the concept of a parallel repressive gene management mechanism being at play in male germ cells at this stage of growth.

The findings, revealed in Nature, present perception in how PGCs regulate their genes within the absence of DNA methylation. And it reveals, for the primary time, that repressive gene regulation is sex-specific at this stage of germline growth.

Revealing vulnerabilities of diseased cells

Dr. Tien-Chi Huang, post-doc in Professor Hajkova’s group and first creator of the paper mentioned: “Epigenetic reprogramming is a highly orchestrated progress during life cycle. Our study provides a long-awaited answer to understand how cells coordinate different layers of controls to maintain gene expression during this process.”

Professor Petra Hajkova, Head of the LMS Reprogramming and Chromatin Research Group mentioned: “These results teach us something fundamental about the control of gene expression. What we have seen looking into the development of embryonic germ cells has a much broader impact because we know a number of human pathologies are characterized by global reduction of DNA methylation. This means our results provide valuable insights into what the diseased cells need to rely on, revealing their potential vulnerabilities.”