Does Selection against Transcriptional Interference Shape Retroelement-Free Regions in Mammalian Genomes?

BACKGROUND: Eukaryotic genomes are scattered with retroelements that proliferate through retrotransposition. Although retroelements make up around 40 percent of the human genome, large regions are found to be completely devoid of retroelements. This has been hypothesised to be a result of genomic regions being intolerant to insertions of retroelements. The inadvertent transcriptional activity of retroelements may affect neighbouring genes, which in turn could be detrimental to an organism. We speculate that such retroelement transcription, or transcriptional interference, is a contributing factor in generating and maintaining retroelement-free regions in the human genome. METHODOLOGY/PRINCIPAL FINDINGS: Based on the known transcriptional properties of retroelements, we expect long interspersed elements (LINEs) to be able to display a high degree of transcriptional interference. In contrast, we expect short interspersed elements (SINEs) to display very low levels of transcriptional interference. We find that genomic regions devoid of long interspersed elements (LINEs) are enriched for protein-coding genes, but that this is not the case for regions devoid of short interspersed elements (SINEs). This is expected if genes are subject to selection against transcriptional interference. We do not find microRNAs to be associated with genomic regions devoid of either SINEs or LINEs. We further observe an increased relative activity of genes overlapping LINE-free regions during early embryogenesis, where activity of LINEs has been identified previously. CONCLUSIONS/SIGNIFICANCE: Our observations are consistent with the notion that selection against transcriptional interference has contributed to the maintenance and/or generation of retroelement-free regions in the human genome

The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations

During development, the mammalian ventral telencephalon is comprised of three major proliferative zones: the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminences. Through gene expression studies, in vitro migration assays, genetic mutant analysis and in vivo fate mapping in mice, we found that the CGE is a progenitor region that is distinct from both the MGE and LGE. Notably, CGE cells showed a unique in vivo pattern of migration, and the CGE contributed cells to nuclei distinct from those populated by the MGE and LGE. Moreover, we report that the migratory fate of cells from the CGE is intrinsically determined by embryonic day 13.5 (E13.5). Together, these results provide the first insights into the development and fate of the CGE

<it>Ascl1 </it>is a required downstream effector of <it>Gsx </it>gene function in the embryonic mouse telencephalon

<p>Abstract</p> <p>Background</p> <p>The homeobox gene <it>Gsx2 </it>(formerly <it>Gsh2</it>) is known to regulate patterning in the lateral ganglionic eminence (LGE) of the embryonic telencephalon. In its absence, the closely related gene <it>Gsx1 </it>(previously known as <it>Gsh1</it>) can partially compensate in the patterning and differentiation of ventral telencephalic structures, such as the striatum. However, the cellular and molecular mechanisms underlying this compensation remain unclear.</p> <p>Results</p> <p>We show here that in the <it>Gsx2 </it>mutants Gsx1 is expressed in only a subset of the ventral telencephalic progenitors that normally express Gsx2. Based on the similarities in the expression of Gsx1 and Ascl1 (Mash1) within the <it>Gsx2 </it>mutant LGE, we examined whether Ascl1 plays an integral part in the <it>Gsx1</it>-based recovery. <it>Ascl1 </it>mutants show only modest alterations in striatal development; however, in <it>Gsx2;Ascl1 </it>double mutants, striatal development is severely affected, similar to that seen in the <it>Gsx1;Gsx2 </it>double mutants. This is despite the fact that <it>Gsx1 </it>is expressed, and even expands, in the <it>Gsx2;Ascl1 </it>mutant LGE, comparable to that seen in the <it>Gsx2 </it>mutant. Finally, Notch signaling has recently been suggested to be required for normal striatal development. In spite of the fact that Notch signaling is severely disrupted in <it>Ascl1 </it>mutants, it actually appears to be improved in the <it>Gsx2;Ascl1 </it>double mutants.</p> <p>Conclusion</p> <p>These results, therefore, reveal a non-proneural requirement of <it>Ascl1 </it>that together with <it>Gsx1 </it>compensates for the loss of <it>Gsx2 </it>in a subset of LGE progenitors.</p