RT Journal
A1 Kikuta, Hiroshi
A1 Laplante, Mary
A1 Navratilova, Pavla
A1 Komisarczuk, Anna Z.
A1 Engström, Pär G.
A1 Fredman, David
A1 Akalin, Altuna
A1 Caccamo, Mario
A1 Sealy, Ian
A1 Howe, Kerstin
A1 Ghislain, Julien
A1 Pezeron, Guillaume
A1 Mourrain, Philippe
A1 Ellingsen, Staale
A1 Oates, Andrew C.
A1 Thisse, Christine
A1 Thisse, Bernard
A1 Foucher, Isabelle
A1 Adolf, Birgit
A1 Geling, Andrea
A1 Lenhard, Boris
A1 Becker, Thomas S.
T1 Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates
JF Genome Research 
JO Genome Research 
YR 2007 
FD May 01 
VO 17 
IS 5 
SP 545 
OP 555 
DO 10.1101/gr.6086307 
UL http://genome.cshlp.org/content/17/5/545.abstract 
AB We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated “bystander” genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs.