Abstract
Vertebrate Pax proteins share a conserved 128-amino-acid DNA-binding motif, the paired domain. The PAX6 gene, which is mutated in the murine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain. This protein, which arises by alternative mRNA splicing, exhibits unique DNA-binding properties. Unlike other paired domains, which bind DNA predominantly by their amino termini, the extended Pax6 paired domain interacts with DNA exclusively through its carboxyl terminus. This property can be simulated by deletion of 30 amino-terminal residues from the Pax6 or Pax2 paired domains. Thus, the insertion acts as a molecular toggle to unmask the DNA-binding potential of the carboxyl terminus. The functional nonequivalence of the two Pax6 proteins is underscored by a T → C mutation at position -3 of the alternative splice acceptor site that changes the ratio of the two isoforms and causes a distinct human ocular syndrome.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2022-2034 |
| Number of pages | 13 |
| Journal | Genes and Development |
| Volume | 8 |
| Issue number | 17 |
| State | Published - Sep 1 1994 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- Developmental Biology
Cite this
Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing. / Epstein, Jonathan A.; Glaser, Thomas M; Cai, Jiexing; Jepeal, Lisa; Walton, David S.; Maas, Richard L.
In: Genes and Development, Vol. 8, No. 17, 01.09.1994, p. 2022-2034.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing
AU - Epstein, Jonathan A.
AU - Glaser, Thomas M
AU - Cai, Jiexing
AU - Jepeal, Lisa
AU - Walton, David S.
AU - Maas, Richard L.
PY - 1994/9/1
Y1 - 1994/9/1
N2 - Vertebrate Pax proteins share a conserved 128-amino-acid DNA-binding motif, the paired domain. The PAX6 gene, which is mutated in the murine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain. This protein, which arises by alternative mRNA splicing, exhibits unique DNA-binding properties. Unlike other paired domains, which bind DNA predominantly by their amino termini, the extended Pax6 paired domain interacts with DNA exclusively through its carboxyl terminus. This property can be simulated by deletion of 30 amino-terminal residues from the Pax6 or Pax2 paired domains. Thus, the insertion acts as a molecular toggle to unmask the DNA-binding potential of the carboxyl terminus. The functional nonequivalence of the two Pax6 proteins is underscored by a T → C mutation at position -3 of the alternative splice acceptor site that changes the ratio of the two isoforms and causes a distinct human ocular syndrome.
AB - Vertebrate Pax proteins share a conserved 128-amino-acid DNA-binding motif, the paired domain. The PAX6 gene, which is mutated in the murine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain. This protein, which arises by alternative mRNA splicing, exhibits unique DNA-binding properties. Unlike other paired domains, which bind DNA predominantly by their amino termini, the extended Pax6 paired domain interacts with DNA exclusively through its carboxyl terminus. This property can be simulated by deletion of 30 amino-terminal residues from the Pax6 or Pax2 paired domains. Thus, the insertion acts as a molecular toggle to unmask the DNA-binding potential of the carboxyl terminus. The functional nonequivalence of the two Pax6 proteins is underscored by a T → C mutation at position -3 of the alternative splice acceptor site that changes the ratio of the two isoforms and causes a distinct human ocular syndrome.
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M3 - Article
C2 - 7958875
AN - SCOPUS:0028096639
VL - 8
SP - 2022
EP - 2034
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 17
ER -