期刊
IMMUNITY
卷 25, 期 5, 页码 717-729出版社
CELL PRESS
DOI: 10.1016/j.immuni.2006.09.007
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资金
- NHLBI NIH HHS [HL07553] Funding Source: Medline
- NIAID NIH HHS [AI035783] Funding Source: Medline
- NIAMS NIH HHS [AR049293] Funding Source: Medline
- NIDDK NIH HHS [DK64400] Funding Source: Medline
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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