Repression of Inappropriate Gene Expression in the Vertebrate Embryonic Ectoderm

During vertebrate embryogenesis, precise regulation of gene expression is crucial for proper cell fate determination. Much of what we know about vertebrate development has been gleaned from experiments performed on embryos of the amphibian Xenopus laevis; this review will focus primarily on studies of this model organism. An early critical step during vertebrate development is the formation of the three primary germ layers—ectoderm, mesoderm, and endoderm—which emerge during the process of gastrulation. While much attention has been focused on the induction of mesoderm and endoderm, it has become clear that differentiation of the ectoderm involves more than the simple absence of inductive cues; rather, it additionally requires the inhibition of mesendoderm-promoting genes. This review aims to summarize our current understanding of the various inhibitors of inappropriate gene expression in the presumptive ectoderm.

RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes

Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1 (PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2 (PRC2) which is required for normal histone H3 lysine 27 trimethylation (H3K27me3). Without normal histone modification-dependent communication between PRC1 and PRC2, repressive Polycomb chromatin domains can erode, rendering target genes susceptible to inappropriate gene expression signals. This suggests that activity-based communication and histone modification-dependent thresholds create a localized form of epigenetic memory required for normal PcG chromatin domain function in gene regulation.

Gene Expression in Neuronal Disease

The brain is the most complex organ of the body and it contains the greatest diversity of cell types. Collectively, the cells within the brain express the greatest number of genes encoded within our genome. Inappropriate gene expression within these cells plays a fundamental role in many neuronal diseases. Illuminating the mechanisms responsible for gene expression is key to understanding these diseases. Because of the complexity, however, there is still much to understand about the mechanisms responsible for gene expression in the brain. There are many steps required for a protein to be generated from a gene, and groups who focus on gene expression normally study a single step such as regulation of transcription, mechanisms of RNA processing or control of translation. To address this, experts were brought together at the Gene Expression in Neuronal Disease meeting in Cardiff. This forum provided the latest insights into specific stages of gene expression in the brain and encompassed the complete pathway from DNA to protein. The present article summarizes the meeting talks and related papers in this issue of Biochemical Society Transactions.