A Distal Conserved Sequence Element Controls Ifng Gene Expression by T Cells and NK Cells
Chromatin dynamics that regulate Ifng gene expression are incompletely understood. By using cross-species comparative sequence analyses, we have identified conserved noncoding sequences (CNSs) upstream of the Ifng gene, one of which, located −22 kb from the transcriptional start site, contains clust...
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Published in: | Immunity (Cambridge, Mass.) Vol. 25; no. 5; pp. 717 - 729 |
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Main Authors: | , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
Elsevier Inc
01-11-2006
Elsevier Limited |
Subjects: | |
Online Access: | Get full text |
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Summary: | Chromatin dynamics that regulate
Ifng gene expression are incompletely understood. By using cross-species comparative sequence analyses, we have identified conserved noncoding sequences (CNSs) upstream of the
Ifng gene, one of which, located −22 kb from the transcriptional start site, contains clustered consensus binding sequences of transcription factors that function in T cell differentiation. CNS−22 was uniquely associated with histone modifications typical of accessible chromatin in both T helper 1 (Th1) and Th2 cells and demonstrated significant and selective T-bet (T-box transcription factor expressed in T cells,
Tbx21)-dependent binding and enhancer activity in Th1 cells. Deletion of CNS−22 in the context of an
Ifng reporter transgene ablated T cell receptor-dependent and -independent
Ifng expression in Th1 effectors and similarly blocked expression by cytotoxic T lymphocytes and natural killer cells. Thus, a single distal element may be essential for
Ifng gene expression by both innate and adaptive immune effector cell lineages. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2006.09.007 |