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3D nuclear organization of chromatin in the embryo after fertilization

Pericentric heterochromatin has been marked with a fluorescent protein. On the left panel, we can see that it normally concentrates around NLBs in the 2-cell stage embryo, forming ring-like structures. On the right panel, researchers managed to link it artificially to the membrane at the nuclear periphery.

Heterochromatin establishment at pericentromeres depends on nuclear position.

Jachowicz JW, Santenard A, Bender A, Muller J, Torres-Padilla ME.

Genes Dev Nov. 15, 2013

Nov. 15, 2013

Upon fertilization the two gametes, the sperm and the oocyte, come together to form a new living organism. The two parental genetic datasets must then acquire a novel configuration with the nucleus to form a competent embryo. For this, both parental genomes undergo reorganization and epigenetic reprogramming. Maria-Elena Torres-Padilla’s team got interested in how chromatin is formed during the very first moments that follow fertilization. In particular, they showed that the spatio-temporal localization of the pericentromeres within the nucleus is an essential factor for proper development. These results are published on 15 November in Genes & Development.


Embryonic chromatin and epigenetic signatures
Within the cell nucleus, DNA is wrapped around proteins called histones and forms the chromatin. It can be very compacted and non-accessible to transcription machinery, which is then called heterochromatin. The non-compacted form permitting transcription is called euchromatin. Both forms differ in epigenetic signatures, which are some chemical modifications appearing on the chromatin (like DNA methylation or histone modifications) and known to be able to regulate the activity of genes. Around the centromere (part of chromosome that links sister chromatids), heterochromatin is composed of repetitive sequences and is called pericentric heterochromatin. These regions are expressed in early embryos to then subsequently become silenced, indicating that the formation of heterochromatin at these genomic domains occurs during early stages of preimplantation development.


Temporal dynamics of pericentric heterochromatin organization and epigenetics signatures acquisition
It was already known that pericentric heterochromatin localization within the nucleus changes during development. In the very first stages of embryogenesis, it concentrates around the nucleoli precursors (NLBs for nucleolar-like-bodies), forming a characteristic ring-like structure. It is only after the late 2-cell stage that chromocentres, which are typical of somatic cells, are formed. Researchers became interested in the chronology of the acquisition of the heterochromatic signatures in the pericentric heterochromatin. Using a fluorescent protein, they observed these marks can be found on pericentromeric regions just after they are located around the NLBs.


About the importance of heterochromatin localization
To know to what extent this organization around NLBs is important for heterochromatin formation at pericentromeres, researchers have then artificially tethered pericentric heterochromatin to the nuclear periphery. They showed that change in its localization increased the transcription of pericentromeric heterochromatin and prevented the acquisition of epigenetic signatures typical of silencing, suggesting that the position around the NLBs play an important role in their silencing. Furthermore, they showed that delocalization of the pericentric heterochromatin from around the nucleoli precursors causes developmental arrest of embryos.


These results are lifting the veil on fundamental mechanisms occurring in the early embryo, suggesting 3D nuclear organization to be one of the crucial factors for heterochromatin formation and epigenetic reprogramming.

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