Building up the nucleus: nuclear organization in the establishment of totipotency and pluripotency during mammalian development

Abstract

In mammals, epigenetic reprogramming, the acquisition and loss of totipotency, and the first cell fate decision all occur within a 3-d window after fertilization from the one-cell zygote to the formation of the blastocyst. These processes are poorly understood in molecular detail, yet this is an essential prerequisite to uncover principles of stem cells, chromatin biology, and thus regenerative medicine. A unique feature of preimplantation development is the drastic genome-wide changes occurring to nuclear architecture. From studying somatic and in vitro cultured embryonic stem cells (ESCs) it is becoming increasingly established that the three-dimensional (3D) positions of genomic loci relative to each other and to specific compartments of the nucleus can act on the regulation of gene expression, potentially driving cell fate. However, the functionality, mechanisms, and molecular characteristics of the changes in nuclear organization during preimplantation development are only now beginning to be unraveled. Here, we discuss the peculiarities of nuclear compartments and chromatin organization during mammalian preimplantation development in the context of the transition from totipotency to pluripotency.Totipotency is the capacity to form all cells in a new organism, including embryonic and extraembryonic tissues. A totipotent zygote is created with the fusion of two highly differentiated cells: the oocyte and the sperm that undergoes epigenetic reprogramming. Upon fertilization, the oocyte completes the second meiotic division, and the maternal chromosomes and the sperm chromatin decondense to form separate pronuclei. The paternal chromatin is quickly assembled into nucleosomes upon removal of the sperm-derived protamines. In contrast, the maternal chromatin inherits a nucleosomal configuration from oogenesis. The subsequent cell divisions are termed cleavages because the size of the daughter cells remains approximately half the size of their mother cells (Aiken et al. 2004). After five divisions, the mouse embryo reaches the blastocyst stage, which is initially composed of the inner cell mass (ICM) and the trophectoderm. While the ICM is pluripotent, the trophectoderm is considered a differentiated, epithelia-like tissue. Thus, the transition from a totipotent state in the zygote to a pluripotent state in the blastocyst occurs in only ∼3 d. Although nuclear size progressively shrinks from the zygote to the blastocyst stage, the nucleocytoplasmic ratio increases due to the cleavage nature of divisions. Another peculiarity of preimplantation development is the inheritance of a large protein pool from the oocyte, which enables the earliest steps of development until the embryo undergoes the maternal-to-zygotic transition and activates its own genome.Nuclear organization refers to the spatial position of nuclear compartments as well as the position that specific regions of the genome adopt with respect to each other and the nuclear compartments. Functionally, increasing evidence suggests that the three-dimensional (...

Three-dimensional analysis of nuclear heterochromatin distribution during early development in the rabbit

“…Indeed, only a few studies have been carried out in the context of early development on bovine or rabbit embryos (Koehler et al 2009; Pichugin et al 2010; Yang et al 2013; Popken et al 2014a, b; review in Borsos and Torres-Padilla 2016). …”

PKC-mediated phosphorylation of nuclear lamins at a single serine residue regulates interphase nuclear size in Xenopus and mammalian cells

“…, 2013; Borsos and Torres-Padilla, 2016), and nuclear size is often inappropriately enlarged in cancer (Zink et al. , 2004; Jevtic and Levy, 2014).…”

EHMT2 and SETDB1 protect the maternal pronucleus from 5mC oxidation

“…Cell functions are governed by gene regulatory mechanisms that include DNA CpG methylation and histone covalent modifications. Both mechanisms undergo global remodeling in the mammalian zygote, together with structural changes (1). The maternally and paternally inherited genomes exhibit asymmetries from the start in the mammalian zygote as a consequence of the differential epigenetic reprogramming during oogenesis and spermatogenesis (2)(3)(4)(5)(6)(7)(8).…”