H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.
Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, but not to other MHC cis-acting sequences or to mutant region II sequences, similar to the naturally occurring region II factor in mouse cells. The deduced amino acid sequence of H-2RIIBP revealed two putative zinc fingers homologous to the DNA-binding domain of steroid/thyroid hormone receptors. Although sequence similarity in other regions was minimal, H-2RIIBP has apparent modular domains characteristic of the nuclear hormone receptors. Further analyses showed that both H-2RIIBP and the natural region II factor bind to the estrogen response element (ERE) of the vitellogenin A2 gene. The ERE is composed of a palindrome, and half of this palindrome resembles the region II binding site of the MHC CRE. These results indicate that H-2RIIBP (i) is a member of the superfamily of nuclear hormone receptors and (ii) may regulate not only MHC class I genes but also genes containing the ERE and related sequences. Sequences homologous to the H-2RIIBP gene are widely conserved in the animal kingdom. H-2RIIBP mRNA is expressed in many mouse tissues, in agreement with the distribution of the natural region II factor.
Hamada
K
K
Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Gleason
S L
SL
Levi
B Z
BZ
Hirschfeld
S
S
Appella
E
E
Ozato
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D015723:Gene Library; D005796:Genes; D005805:Genes, MHC Class I; D005809:Genes, Regulator; D008099:Liver / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D011956:Receptors, Cell Surface / Q000235:genetics; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D011956:Receptors, Cell Surface; C061606:Rxrb protein, mouse