Possible involvement of SINEs in mammalian-specific brain formation

Abstract

Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalianspecific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.conserved noncoding element ͉ enhancer ͉ evolution ͉ mouse

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

“…3C). This level of identity is similar to those found among orthologous nPE1 sequences from distantly related mammals, such as the elephant and the tenrec (Table S1), and to other recently reported cases of mobile elements exapted into functional enhancers (17,20,21).…”

“…nPE2 (blue arrow) appeared in the lineage leading to mammals, and nPE1 (purple arrow) is found only in placental mammals. similar to those reported for the opossum nPE2 and a consensus CORE-SINE [59% along 70 bp, with a central 45-bp region showing 71% identity (17)], the human ISL1 enhancer and consensus LF-SINE [61% along 55 bp (20)], and the consensus Amn-SINE and human Fgf8 enhancer [70% identity along 170 bp (21)]. Interestingly, a MaLR of the MSTB2 family was recently reported to have been exonized into an alternatively spliced exon of the IL22RA2 gene in primates (34).…”

“…Although it is conceivable that most conserved retroelement-derived sequences located in the vicinity of transcriptional units play some role in gene expression regulation, functional proof of exapted regulatory retroelements has been scarcely demonstrated. Indeed, nPE1 may be added to the incipient list of ancient retroposons coopted into cell-specific enhancers that includes three different types of SINEs: an LF-SINE exapted into an enhancer of Isl1 (20), a CORE-SINE exapted into the neuronal Pomc enhancer nPE2 (17), and an AmnSINE1 that evolved into a brain Fgf8 enhancer (21). Evidence that nPE1 derives from the exaptation of a MaLR is based on the high percentage of identity between human nPE1 and THE1B (62% along the 160 bp of nPE1core).…”

Co-option of Sox3 as the male-determining factor on the Y chromosome in the fish Oryzias dancena

“…It has been proposed that insertions of such transposable elements are potential sources of new cis-regulatory elements 47,48 and long non-coding RNAs 49,50 . Transposable elements are abundant in vertebrate genomes, and some of them have been shown to function as cis-regulatory elements of specific genes [51][52][53] . It is also possible that in O. dancena, the Y chromosome-specific insertion or accumulation of repetitive elements has served as the distant cis-regulatory sequence driving Sox3 expression.…”

Alu-derived cis-element regulates tumorigenesis-dependent gastric expression of GASDERMIN B (GSDMB)

“…Alu elements are present in more than one million copies and can represent over 10% of wholegenome mass (The BAC Resource Consortium, 2001). Some Alu elements are known to reside in the 5'-flanking regions of genes or within genes and to affect expression of relevant genes in human and mouse (Ferrigno et al, 2001;Batzer and Deininger 2002;Sasaki et al, 2008). The reporter assays in this study showed that deletion of the whole Alu element did not completely abolish GSDMB expression.…”