title: Lability of leukosis virus enhancer-binding proteins in avian hematopoeitic cells.
abstract: Bursal lymphomas induced by avian leukosis virus (ALV) are characterized by integration of long terminal repeat (LTR) enhancer sequences next to the myc proto-oncogene and by subsequent myc hyperexpression. Nuclear runoff transcription analyses have shown that protein synthesis inhibition specifically decreases transcription of LTR-enhanced genes in bursal lymphoma cell lines (M. Linial, N. Gunderson, and M. Groudine, Science 230:1126-1132, 1985). Here, we show that LTR-enhanced transcription is also labile in nontransformed bursa, bone marrow, and spleen but not in other ALV-infected tissues from lymphoma-susceptible chickens. The bursal cells demonstrated this lability of LTR-enhanced transcription only at an early stage of development, when chickens are susceptible to ALV-induced lymphomagenesis. Mature bursal cells show stable LTR transcription enhancement (unaffected by inhibition of protein synthesis) and are not susceptible to lymphomagenesis. In lymphoma-resistant chicken strains, LTR-enhanced transcription was stable in all tissues during development. These data suggest that lability of LTR transcription enhancement in hematopoietic cells is involved in susceptibility to lymphomagenesis, and we propose a model for the action of these labile enhancing factors. Gel shift analysis of nuclear proteins from lymphoma cells indicated that four or more binding proteins specifically interact with the three LTR enhancer regions. These proteins can be separated by their differential sensitivity to heat treatment or protein synthesis inhibition. The lability of a subset of these binding proteins correlates with lability of LTR-enhanced transcription in certain lymphoid cell types, suggesting that these proteins are essential for LTR transcription enhancement.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
authors.forename: A
authors.initials: A
authors.lastname: Ruddell
authors.forename: M
authors.initials: M
authors.lastname: Linial
authors.forename: W
authors.initials: W
authors.lastname: Schubach
authors.forename: M
authors.initials: M
authors.lastname: Groudine
mesh_terms: D000818:Animals; D002645:Chickens; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D008223:Lymphoma / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D001356:Reticuloendotheliosis virus / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors