Symmetry from Asymmetry or Asymmetry from Symmetry?

The processes of DNA replication and mitosis allow the genetic information of a cell to be copied and transferred reliably to its daughter cells. However, if DNA replication and cell division were always performed in a symmetric manner, the result would be a cluster of tumor cells instead of a multicellular organism. Therefore, gaining a complete understanding of any complex living organism depends on learning how cells become different while faithfully maintaining the same genetic material. It is well recognized that the distinct epigenetic information contained in each cell type defines its unique gene expression program. Nevertheless, how epigenetic information contained in the parental cell is either maintained or changed in the daughter cells remains largely unknown.

the inherent asymmetry of DNA replication and the increasing knowledge about the polarity in mitosis raise some questions. Further research will explore whether symmetric outcomes arise from tightly regulated asymmetric molecular and cellular processes, or whether symmetry is the default pathway and is then broken by asymmetric processes.

In reality, both symmetric and asymmetric outcomes are required to build up a multicellular organism originating from a single cell, a fertilized egg, to produce an individual human being made up of hundreds of cell types. Even though most cells in our bodies carry identical DNA sequences, only a subset of these sequences turn on expression at the proper time, in the right place, and with the precise level during development and homeostasis.

It is well recognized that the distinct epigenetic information contained in each cell type defines its unique gene expression program. However, how the epigenetic information contained in the parental cell can be maintained, or changed, in the daughter cells remains largely unknown. This question is extremely difficult to address because the epigenome is composed of numerous components that dynamically change their composition. Nonetheless, this question is central to our understanding of the fundamental principles of biology and our ability to develop new treatments against human diseases including birth defects, neurodegenerative disease, tissue dystrophy, infertility, and cancers.

Asymmetric histone inheritance could represent the mechanism that maintains equilibrium between the rigidity of genetic information and the plasticity of epigenetic information. We anticipate that future work will address whether this mechanism is used at specific gene loci for differential gene expression upon ACD and whether this mechanism is also applicable to other cell types or in other organisms.