The REST protein helps to prevent the premature activation of genes that are only expressed in mature neurons, and is now found to protect the genome of neural progenitor cells. is built up one layer at a time. This is achieved by controlling how cells called apical progenitors become basal progenitors, which then specialize into new neurons (Gotz et al., 2002; Figure 1). If the apical progenitors become basal progenitors too soon, several developmental brain abnormalities can result, the brain may be too small (a condition known as microcephaly), or the layering of the cortex may be disrupted. Now, in eLife, Gail Mandel of the Oregon Health and Science University and co-workers C including Tamilla Neichiporuk as first author C report that a protein called REST has an unexpected role in protecting the genome of these progenitor cells (Nechiporuk et al., 2016). Open in a separate window Figure 1. REST regulation in embryonic neurogenesis.The REST protein is expressed in apical progenitors (green cells) and represses the expression of genes that are necessary for neurons (pink cell) to develop. Left: REST maintains genome stability, protecting the DNA of the apical progenitor cell during S phase (the phases of the cell cycle are Bmpr1b shown in the yellow and white oval). The cells then reduce the production of REST precisely at the apical progenitor cell cycle exit (during G1 phase). This ensures that new neurons develop properly. Right: In the absence of REST, the DNA of the apical progenitor cell becomes damaged during S phase, PF-562271 kinase activity assay preventing the subsequent production of basal progenitors and neurons. The identity of a cell is determined to a large extent by which of its genes are transcribed. Therefore, when a new neuron first develops from a progenitor cell, a process of ‘transcriptional resetting’ must occur so that the genes that need to be expressed in mature neurons can be activated. The REST protein, first identified in 1995, can be expressed in every cells aside from mature neurons, therefore researchers instantly suspected that it had been involved with repressing neuronal genes (Schoenherr and Anderson, 1995; Chen et al., 1998; Bruce et al., 2004). Support because of this idea originated from tests that demonstrated that REST binds to and represses hereditary components that are connected with many genes that are particular to adult neurons. Within this repression, REST recruits some repressor complexes that alter the way the gene can be packed right into a framework called chromatin. Nevertheless, a previous research concerning knockout mice who cannot produce the others proteins failed to determine any significant abnormalities in the developing or adult mind (Gao et al., 2011; Aoki et al., 2012: Yang et al, 2012). The role of REST has remained uncertain. Nechiporuk et al. C who are located in the united states and Germany C have finally used a method called conditional hereditary ablation to explore the part of REST in neural progenitors. This exposed an unexpected requirement of REST in safeguarding the genome from the apical progenitors. Lack of REST induces PF-562271 kinase activity assay DNA harm during?the S phase from the cell cycle: this is actually the phase where DNA is replicated. A rsulting consequence this harm may be the acquisition of chromosomal abnormalities in the apical progenitors. This causes cells to commit suicide C PF-562271 kinase activity assay following a orders of the proteins known as p53 C and the effect can be microcephaly. Nechiporuk et al. also display that the mixed lack of REST and p53 leads to the formation of a highly aggressive brain tumour called a glioblastoma. REST therefore performs a dual role during brain development: it protects the progenitor cells from genetic catastrophe, and it silences neuronal gene expression until the time is right. These findings came as.