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Chromatin, an acute controller of cell cycle

The role of PR-Set7 in replication licensing depends on Suv4-20h.

Beck DB, Burton A, Oda H, Ziegler-Birling C, Torres-Padilla ME, Reinberg D.

Genes Dev Nov. 14, 2012

Nov. 15, 2012

Collaborative studies by Maria-Elena Torres-Padilla team at the IGBMC and the laboratory of Danny Reinberg team at the Howard Hughes Medical Institute from the New-York University, are bringing to light mechanisms of cell cycle regulation by two histone methyltransferases that control the degree of chromatin condensation. Their results also demonstrate some specificities of the early mammalian embryo. These results are published on 14th November 2012 in Genes & Development.

DNA and cell cycle

The cell cycle includes a series of stages that the cell goes through between two divisions. Throughout this cycle, the genetic information changes its organisation within the nucleus. During mitosis (the division of one cell into two identical daughter cells), the DNA is highly compacted to form the chromosomes, in contrast the DNA is more condensed and located in the nucleus during the interphase (period between two mitosis).


Different states of chromatin dependent on methylation

In the nucleus, the DNA is found in a nucleoproteic complex called chromatin. The chromatin exists in two types of states: euchromatin consists of accessible and active DNA, whereas heterochromatin is composed of tightly packed and inactive DNA. The euchromatin and heterochromatin are defined according to methylation status present on their histones, the proteins around which the DNA wrapped. These two chromatin states can regulate cell cycle progression. Researchers within Maria-Elena Torres-Padilla and Danny Reinberg teams have focused on histone methylation, and in particular methylation of histone H4, which accurs at three different levels: mono-, di- and tri-methylation. The enzyme PRset7 is responsible for mono-methylation of H4, while Suv4-20 enables the di- and tri-methylation. They notably showed that the first methylation is involved in the regulation of DNA replication (doubling of the genetic information during interphase, before cell division). On the whole, a dysfunction of the coordinated action of these two enzymes provokes DNA damage by affecting the cell cycle.


A different functioning in the early embryo

The same teams had already observed that deletion of PRset7 in embryo did not provoke DNA damage, contrary the situation in stem cells, and this had suggested a specific chromatin configuration in the early embryo. In this new study, researchers have introduced Suv4-20 by microinjection, in order to artificially compact chromatin into heterochromatin. They saw that the early embryo was thus presenting DNA damage and could stop its development in the absence of PRset7.


These results are bringing new light on the mechanisms that regulate mechanisms cell cycle progression and the correct DNA synthesis. They suggest a different feature in the early mammalian embryo. The comprehension of these specific features is essential to better understand the protection mechanisms of the DNA in the embryo, necessary for its proper development after fertilization and before its implantation into the uterus.


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