Epigenetic reprogramming and development: a unique heterochromatin organization in the preimplantation mouse embryo

Abstract

Fertilization of the oocyte by the sperm results in the formation of a totipotent zygote, in which the maternal and paternal chromatin is enclosed in two pronuclei undergoing distinct programmes of transcriptional activation and chromatin remodelling. The highly packaged paternal chromatin delivered by the sperm is decondensed and acquires a number of specific epigenetic marks, but markedly remains devoid of those usually associated with constitutive heterochromatin. During this period the maternal chromatin remains relatively stable except for marks associated with transcription and/or replication such as arginine methylation and H3/H4 acetylation. The embryo then undergoes a series of mitotic divisions without significant additional growth but differentiation, resulting in the formation of a blastocyst containing distinct cell types. The chromatin remodelling events during these stages are likely to be important in establishing the nuclear foundations required for later triggers of differentiation. Overall, we summarize three important points during these earliest reprogramming events: (i) relatively stable maternal chromatin after fertilization, (ii) rapid acquisition of specific histone marks by the paternal chromatin during the hours that follow fertilization and (iii) rapid remodelling of constitutive heterochromatic marks and modifications in the core of the nucleosome from the first mitotic division. These features are likely to be required for the creation of a chromatin environment compatible with cellular reprogramming and plasticity.