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The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated

Journal Article · · Mol. Cell. Biol.; (United States)
DOI:https://doi.org/10.1128/MCB.8.2.930· OSTI ID:7242440
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Previous studies have indicated that immunoglobulin enhancers are essential for establishing transcriptional competence but not for maintaining the activity of constitutively transcribed genes. To understand the basis for this developmental shift away from dependence on enhancer function, the authors investigated the relationship between transcriptional activity and methylation status of the immunoglobulin kappa-light-chain genes (kappa genes) in mouse cell lines representing different stages of B-cell maturation. Using pre-B-cell lines in which the level of a critical kappa enhancer-binding factor, NF-kappaB, was controlled by the administration of withdrawal of lipopolysaccharide and plasmacytoma lines that either contain or lack this factor, they studied the properties of endogenous kappa genes and of transfected kappa genes which were stably integrated into the genomes of these cells. In the pre-B cells, the exogenous (originally unmethylated) kappa genes, as well as the endogenous kappa genes, were fully methylated and persistently dependent on enhancer function, even after more than 30 generations in a transcriptionally active state. In plasmacytoma cells, the endogenous kappa genes were invariably hypomethylated, whereas exogenous kappa genes were hypomethylated only in cells that contain NF-kappaB and are thus permissive for kappa enhancer function. These results indicate that the linkage of hypomethylation to enhancer-dependent activation of kappa transcription occurs after the pre-B-cell stage of development. The change in methylation status, together with associated changes in chromatin structure, may suffice to eliminate or lessen the importance of the enhancer for the maintenance of the transcriptionally active state.
Research Organization:
Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111 (US)
OSTI ID:
7242440
Journal Information:
Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 8:2; ISSN MCEBD
Country of Publication:
United States
Language:
English

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Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CULTURES
CHEMICAL REACTIONS
CHROMATIN
CONNECTIVE TISSUE CELLS
GENE AMPLIFICATION
GENE REGULATION
GENES
GLOBULINS
IMMUNOGLOBULINS
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
METHYLATION
MICE
ORGANIC COMPOUNDS
PROTEINS
RODENTS
SOMATIC CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION
VERTEBRATES