Genetic and Epigenetic Regulators of Pluripotency

Abstract

Genetic and epigenetic mechanisms regulate the transition from the totipotent zygote to pluripotent primitive ectoderm cells in the inner cell mass of mouse blastocysts. These pluripotent cells can be propagated indefinitely in vitro, underpinned by a unique epigenetic state. Following implantation of the blastocyst, diverse epigenetic modifiers control differentiation of pluripotent epiblast cells into somatic cells, while specification of germ cells requires repression of the somatic program. Regenerating totipotency during development of germ cells entails re-expression of pluripotency-specific genes and extensive erasure of epigenetic modifications. Increasing knowledge of key underlying mechanisms heightens prospects for creating pluripotent cells directly from adult somatic cells.

Histone deacetylases 1 and 2 are expressed at distinct stages of neuro‐glial development

“…Epigenetic regulation-histone and DNA modifications that influence the repertoire of genes that can be expressed in a cell-is a key process in development (Jaenisch and Bird, 2003;Margueron et al, 2005;Surani et al, 2007). Modifications of the Nterminal domains of core histone proteins, including methylation and acetylation, regulate chromatin structure and gene expression (Strahl and Allis, 2000;Turner, 2000;Jenuwein and Allis, 2001).…”

Incomplete penetrance and variable expressivity: is there a microRNA connection?

“…Epigenetic regulators like DNA and histone methyltransferases are also included under this category. (40) Consequently, it follows that the wild-type or normal alleles of genes are also influenced by these interacting factors. However, when there are no mutations affecting the functional protein, the cell achieves a steady-state level of normal protein required for the function and, hence, manifests normal phenotype.…”

“…The sequences of genes listed by Surani et al as modifier genes were retrieved from ENSEMBL. (40) A representative list of genes is given in Table 1 and the complete list is given in Supporting Information Table 1. We generated a list of 143 genes implicated in autosomal single gene disorders that show incomplete or reduced penetrance and/or variable expressivity and screened them for the presence of putative miRNA binding sites in their 3 0 UTR.…”

“…(55) In the former case, miRNA and its target mRNA Number of genes retrieved from OMIM showing IP-VE. c Number of modifier genes taken from Surani et al (40) d Number of house-keeping genes used as control set (67) ( p value<0.05 IP-VE to control).…”

“…Thirty-one epigenetic modifiers reported by Surani et al were taken; (40) and their human orthologs were taken from HomoloGene, NCBI. The list of housekeeping genes used as control was taken from Eisenberg and Levanon.…”