Deletion of a conserved noncoding sequence in Plzf intron leads to Plzf down-regulation in limb bud and polydactyly in the rat
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
19191224
DOI
10.1002/dvdy.21859
Knihovny.cz E-zdroje
- MeSH
- delece genu MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- down regulace genetika MeSH
- embryo savčí embryologie metabolismus MeSH
- introny genetika MeSH
- končetinové pupeny abnormality metabolismus MeSH
- konzervovaná sekvence MeSH
- krysa rodu Rattus MeSH
- messenger RNA genetika MeSH
- nekódující RNA genetika MeSH
- polydaktylie genetika metabolismus MeSH
- protein promyelocytické leukemie s motivem zinkového prstu MeSH
- rozvržení tělního plánu MeSH
- sekvence nukleotidů MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- messenger RNA MeSH
- nekódující RNA MeSH
- protein promyelocytické leukemie s motivem zinkového prstu MeSH
- ZBTB16 protein, rat MeSH Prohlížeč
Lx mutation in SHR.Lx rat manifests in homozygotes as hindlimb preaxial polydactyly. It was previously mapped to a chromosome 8 segment containing the Plzf gene. Plzf (promyelocytic leukemia zinc finger protein) influences limb development as a direct repressor of posterior HoxD genes. However, the Plzf coding sequence is intact in the Lx mutants. Using linkage mapping in F2 hybrids, we downsized the segment containing Lx to 155 kb and sequenced conserved noncoding elements (CNEs) inside. A 2,964-bp deletion in Plzf intron 2, never detected in control animals, is the only candidate for Lx. The deletion removes the most deeply conserved CNE in the 155-kb segment, suggesting a regulatory influence on Plzf expression. Correspondingly, using in situ hybridization and quantitative real-time polymerase chain reaction, we found a decrease of Plzf expression in Lx/Lx limb buds with concomitant anterior expansion of expression domains of its targets, Hoxd10-13 genes, in the absence of ectopic Sonic hedgehog expression. Upstream regulation of Plzf in limb buds is currently unknown. We present here the first candidate Plzf cis-regulatory sequence.
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