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Embryonic histone H1 (in red) , dBigH1, regulates zygotic genome activation (S.Pérez; IRB).

In the beginning was Histone 1

In the fly Drosophila, a team of scientists at IRB Barcelona have identified a protein essential to embryo viability in its first cell divisions. dBigH1 is a protein variant of histone 1, and is also associated with fertility.

A zygote is the first cell of a new individual that comes into existence with the fusion of an egg and a sperm. The DNA of the zygote holds all the information required to generate an adult. However, during embryogenesis—the first stages of life—the genome of the zygote does not 'turn on'.

In the fly Drosophila melanogaster, the genes of the zygote are repressed until the thirteenth division, after which they start to express. Ferran Azorín, CSIC Research professor, has identified the dBigHi protein in Drosophila that keeps the zygote genome inactive until the correct moment.

Without dBigHi, the genome is switched on too early and the embryo dies.

Research results are published in Developmental Cell.

This is the first time that scientists have described a specific function for histone 1 during embryogenesis. Although this protein was known to be present in the first embryonic stages of humans as well as mice, until now nothing was known about its function.

“The fact that now we have also detected this protein in Drosophila has allowed us to study its vital activity during early stages of embryo development more efficiently,” explains Salvador Pérez-Montero, PhD student and first author of the study. Albert Carbonell, postdoctoral researcher joined the project a year ago. “If this same function is conserved in humans, its alteration could be related to gestational disorders—or early miscarriage,” adds Ferran Azorín, head of the group.

Dr. Azorín goes on to explain that “these are not disorders—in the true sense— that are commonly treated and, problems during gestation can arise for many different reasons.”

dBigH1 may also be related to male and female fertility. As this study has revealed that the molecule plays a fundamental role in fly embryogenesis, the researchers are now focusing on defining the function dBigH1 plays in germ (sex) cells.

The germline is made up of the sex cells, the cells that give rise to eggs (ovules) and sperm (spermatozoids), the very cells responsible for passing down genetic information from one generation to another. In the Drosophila embryo, all of the germ cells express the protein dBigH1.

The first functional results point to dBigH1 regulating sperm production in males and egg (ovule) production in females. “When this gene is removed, this process is totally disrupted,” explain the researchers.

The next paper is expected to reveal whether there is indeed a relationship between the protein dBigH1 and individual fertility.

Abstract
Highlights
CG3509 encodes the embryonic H1 of Drosophila, dBigH1
dBigH1 is replaced by somatic dH1 at cellularization in somatic cells
dBigH1 is retained in the germline cells through development
dBigH1 regulates zygotic genome activation in the soma and the germline
Summary

Histone H1 is an essential chromatin component. Metazoans usually contain multiple stage-specific H1s. In particular, specific variants replace somatic H1s during early embryogenesis. In this regard, Drosophila was an exception because a single dH1 was identified that, starting at cellularization, is detected throughout development in somatic cells. Here, we identify the embryonic H1 of Drosophila, dBigH1. dBigH1 is abundant before cellularization occurs, when somatic dH1 is absent and the zygotic genome is inactive. Upon cellularization, when the zygotic genome is progressively activated, dH1 replaces dBigH1 in the soma, but not in the primordial germ cells (PGCs) that have delayed zygotic genome activation (ZGA). In addition, a loss-of-function mutant shows premature ZGA in both the soma and PGCs. Mutant embryos die at cellularization, showing increased levels of active RNApol II and zygotic transcripts, along with DNA damage and mitotic defects. These results show an essential function of dBigH1 in ZGA regulation.

Reference article:
The Embryonic Linker Histone H1 Variant of Drosophila, dBigH1, Regulates Zygotic Genome Activation
Salvador Pérez-Montero, Albert Carbonell, Tomás Morán, Alejandro Vaquero, and Fernando Azorín.
Developmental Cell (2013), http://dx.doi.org/10.1016/j.devcel.2013.08.011

Ferran Azorín is also CSIC Research professor, the Chromatin Structure and Function group at the IRB Barcelona

Original press releas: http://www.irbbarcelona.org/index.php/en/news/irb-news/scientific/and-in-the-beginning-was-histone-1