A cis element in the recombination activating gene locus regulates gene expression by counteracting a distant silencer.
We have identified a silencer and an antisilencing element that interact at a distance of 85 kilobases to regulate expression of the recombination activating genes Rag1 and Rag2 in thymocytes. Transgenic experiments showed that Rag promoter-proximal cis elements directed tissue-specific expression and that a Runx-dependent intergenic silencer suppressed expression in developing T cells. Deletion of the antisilencing element from the genomic Rag locus unmasked the intergenic silencer and abrogated Rag expression in developing CD4(+)CD8(+) T cells. We speculate that the Rag antisilencing element belongs to a class of cis elements that might be useful for genome diversification by activating genes encoded by otherwise silent transposable elements.
Yannoutsos
Nikos
N
Laboratory of Molecular Immunology, Rockefeller University, New York, New York 10021, USA. yannou@rockvax.rockefeller.edu
Barreto
Vasco
V
Misulovin
Ziva
Z
Gazumyan
Anna
A
Yu
Wong
W
Rajewsky
Nikolaus
N
Peixoto
Bernardo R
BR
Eisenreich
Thomas
T
Nussenzweig
Michel C
MC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D016654:Genes, RAG-1; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017384:Sequence Deletion; D037941:Silencer Elements, Transcriptional; D013950:Thymus Gland / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C499308:Rag2 protein, mouse; C493726:Runx1 protein, mouse; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2