TY - JOUR
T1 - Evolutionarily assembled cis-regulatory module at a human ciliopathy locus
AU - Lee, Jeong Ho
AU - Silhavy, Jennifer L.
AU - Lee, Ji Eun
AU - Al-Gazali, Lihadh
AU - Thomas, Sophie
AU - Davis, Erica E.
AU - Bielas, Stephanie L.
AU - Hill, Kiley J.
AU - Iannicelli, Miriam
AU - Brancati, Francesco
AU - Gabriel, Stacey B.
AU - Russ, Carsten
AU - Logan, Clare V.
AU - Sharif, Saghira Malik
AU - Bennett, Christopher P.
AU - Abe, Masumi
AU - Hildebrandt, Friedhelm
AU - Diplas, Bill H.
AU - Attié-Bitach, Tania
AU - Katsanis, Nicholas
AU - Rajab, Anna
AU - Koul, Roshan
AU - Sztriha, Laszlo
AU - Waters, Elizabeth R.
AU - Ferro-Novick, Susan
AU - Woods, C. Geoffrey
AU - Johnson, Colin A.
AU - Valente, Enza Maria
AU - Zaki, Maha S.
AU - Gleeson, Joseph G.
PY - 2012/2/24
Y1 - 2012/2/24
N2 - Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.
AB - Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.
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U2 - 10.1126/science.1213506
DO - 10.1126/science.1213506
M3 - Article
C2 - 22282472
AN - SCOPUS:84862776586
SN - 0036-8075
VL - 335
SP - 966
EP - 969
JO - Science
JF - Science
IS - 6071
ER -