title: Selective loss of a DNase I hypersensitive site upstream of the tyrosine aminotransferase gene in mice homozygous for lethal albino deletions.
abstract: Several overlapping chromosomal deletions spanning the albino locus in the mouse cause perinatal lethality when homozygous and a block in the transcriptional induction of various unlinked hepatocyte-specific genes. Studies of such lethal albino deletion homozygotes in perinatal stages revealed a deficiency in the transcriptional inducibility of the tyrosine aminotransferase (TAT) gene by glucocorticoids; yet, glucocorticoid receptor and hormone levels were shown to be unaffected. To identify a molecular defect underlying the failure of inducible expression, we examined the chromatin structure of the TAT gene. Whereas in wild-type animals the TAT promoter becomes DNase I hypersensitive at birth, such hypersensitivity fails to develop in lethal albino deletion homozygotes. By contrast, the deletions do not affect the appearance of three DNase I-hypersensitive sites upstream of the TAT promoter in the liver, nor do they affect two hypersensitive sites upstream of the expressed alpha-fetoprotein gene. These findings demonstrate that the abnormality of chromatin structure identified in lethal albino deletion homozygotes occurs on a highly selective basis. Specifically, normal differentiation of the TAT promoter chromatin appears to depend directly or indirectly on the action and product of a gene mapping within the deleted region.
authors.affiliation: Section of Biochemistry, Brown University, Providence, RI 02912.
authors.forename: K S
authors.initials: KS
authors.lastname: Zaret
authors.forename: P
authors.initials: P
authors.lastname: Milos
authors.forename: M
authors.initials: M
authors.lastname: Lia
authors.forename: D
authors.initials: D
authors.lastname: Bali
authors.forename: S
authors.initials: S
authors.lastname: Gluecksohn-Waelsch
mesh_terms: D000417:Albinism / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D003850:Deoxyribonuclease I; D015971:Gene Expression Regulation, Enzymologic; D005804:Genes, Lethal; D008099:Liver / Q000196:embryology / Q000201:enzymology; D051379:Mice; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D014444:Tyrosine Transaminase / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: D000509:alpha-Fetoproteins; D014444:Tyrosine Transaminase; D003850:Deoxyribonuclease I