TY  - JOUR
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
Y1  - 2007/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 545 
EP  - 555 
DO  - 10.1101/gr.6086307 
VL  - 17 
IS  - 5 
UR  - http://genome.cshlp.org/content/17/5/545.abstract 
N2  - 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. 
ER  -