Dr. Tjian is also Professor of Molecular and Cell 
Biology at the University of California, Berkeley, 
and Adjunct Professor of Biochemistry and 
Biophysics at the University of California, San 
Francisco. 
Articles 
Baichwal, V.R., Park, A., and Tjian, R. 1992. The 
cell-type-specific activator region of c-jun juxta- 
poses constitutive and negatively regulated do- 
mains. Genes Dev 6:\A95-\502. 
Comai, L., Tanese, N., and Tjian, R. 1992. The 
TATA-binding protein and associated factors are 
integral components of the RNA polymerase I 
transcription factor, SLl. Ce// 68:965-976. 
England, B.P., Admon, A., and Tjian, R. 1991. 
Cloning of Drosophila transcription factor Adf- 1 
reveals homology to Myb oncoproteins. Proc Natl 
Acad Sci USA 89:683-687. 
Gill, G., and Tjian, R. 1992. Eukaryotic coactivators 
associated with the TATA binding protein. Curr 
Opin Genet Dev 2:236-242. 
Pascal, E., and Tjian, R. 1991. Different activation 
domains of Spl govern formation of multimers 
and mediate transcriptional synergism. Genes 
Dev 5:1646-1656. 
Peterson, M.G., Inostroza, J., Maxon, M.E., Flores, 
O. , Admon, A., Reinberg, D. , and Tjian, R. 1 99 1 . 
Structure and functional properties of human gen- 
eral transcription factor HE. Nature 354:369- 
373. 
Pugh, B.F., and Tjian, R. 1 99 1 . Transcription from a 
TATA-less promoter requires a multisubunit 
TFIID complex. Genes Dev 5:1935-1945. 
Pugh, B.F., and Tjian, R. 1992. Diverse transcrip- 
tional functions of the multisubunit eukaryotic 
TFIID complex./ 5/0/ Chem 267:679-682. 
Tanese, N., Pugh, B.F., and Tjian, R. 1991. Coacti- 
vators for a proline-rich activator purified from 
the multisubunit human TFIID complex. Genes 
Dev 5:2212-2224. 
GENETIC DEFECTS IN THE METABOLIC PATHWAYS INTERCONNECTING 
THE UREA AND TRICARBOXYLIC ACID CYCLES 
David L. Valle, M.D., Investigator 
The general theme of Dr. Valle's research is hu- 
man genetic diseases, particularly disorders of 
amino acid metabolism, retinal degenerations, and 
inborn errors of peroxisome biogenesis. During the 
past year he has continued to work on an inborn 
error of amino acid metabolism that produces a reti- 
nal degeneration, gyrate atrophy of the choroid and 
retina (GA). This rare, autosomal recessive, blind- 
ing disorder is characterized biochemically by or- 
nithine accumulation and results from inherited de- 
fects in ornithine-6-aminotransferase (OAT) . 
As an extension of this research, Dr. Valle and his 
colleagues are cloning and characterizing other 
genes whose expression is important for the normal 
function of retinal photoreceptors. They are also 
studying a group of closely related genetic disorders 
characterized by abnormal peroxisome formation. 
Peroxisomes are spherical, single membrane-bound 
organelles containing >40 matrix enzymes that are 
involved in a variety of oxidative and synthetic pro- 
cesses. Zellweger syndrome (ZS), a genetically het- 
erogeneous, autosomal recessive, lethal disorder, is 
the clinical paradigm for inborn errors of peroxiso- 
mal biogenesis. 
Ornithine-6- Aminotransferase 
Analysis of the OAT mutations in GA. Dr. 
Valle and his colleagues have now identified 37 
mutant OAT alleles. Together with 10 mutant 
OAT alleles reported by other groups, these mu- 
tations account for about two-thirds of all the pos- 
sible 1 74 abnormal alleles in the probands of the 
87 GA pedigrees being analyzed in Dr. Valle's 
laboratory. 
One recently recognized OAT allele of particular 
interest, A226V, may be important for understand- 
ing the molecular basis of vitamin-responsive in- 
born errors. The mutant enzyme responds to high 
concentrations of pyridoxal phosphate both in vivo 
and in vitro. The amino acid substitution is four 
residues upstream of E230, which is predicted on 
the basis of homology to another pyridoxal phos- 
phate-dependent enzyme to interact with Nl of the 
pyridoxal phosphate molecule. A second recently 
recognized OAT allele was detected in several 
members of a large Italian kindred and results from 
the deletion of a 5'-untranslated sequence, leaving 
the translated portion of the OAT mRNA intact. De- 
spite this, the mutation appears to block translation 
278 
