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Your search keyword '"Pérez-Melgosa, Mercedes"' showing total 6 results
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4. Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells.

Author

Makar, Karen W., Pérez-Melgosa, Mercedes, Shnyreva, Maria, Weaver, William M., Fitzpatrick, David R., and Wilson, Christopher B.

Subjects
*INTERLEUKIN-4, *METHYLTRANSFERASES, *DNA, *T cells
Abstract

How T cells regulate interleukin 4 (IL-4) expression is not completely understood. We show here that single-positive thymocytes express IL-4, but attenuate GATA-3 expression, recruit DNA methyltransferases (Dnmts) to the Il4-Il13 locus and downregulate IL-4 expression as they mature into T cells. Type 2 polarization blocks Dnmt1 recruitment, enhances histone H3 Lys4 methylation (indicative of accessible chromatin) and initiates DNA demethylation of the locus. Dnmt1-/- CD4 and CD8 T cells derepress IL-4 expression considerably, demethylate DNA and increase H3 Lys4 methylation without affecting GATA-3 expression, demonstrating that Dnmt1 and DNA methylation are essential for proper Il4 regulation. These results indicate that Dnmts, DNA and histone methylation, and transcription factors 'collaborate' to determine appropriate Il4 expression patterns. [ABSTRACT FROM AUTHOR]

Published
2003
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6. CCCTC-binding factor and the transcription factor T-bet orchestrate T helper 1 cell-specific structure and function at the interferon-gamma locus.

Author

Sekimata M, Pérez-Melgosa M, Miller SA, Weinmann AS, Sabo PJ, Sandstrom R, Dorschner MO, Stamatoyannopoulos JA, and Wilson CB

Subjects
Animals, CCCTC-Binding Factor, CD4-Positive T-Lymphocytes metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins immunology, Cell Cycle Proteins metabolism, Cells, Cultured, Chromatin immunology, Chromatin metabolism, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone immunology, Chromosomal Proteins, Non-Histone metabolism, Humans, Interferon-gamma genetics, Interferon-gamma immunology, Interleukins genetics, Interleukins immunology, Interleukins metabolism, Introns genetics, Introns immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Rats, Repressor Proteins genetics, Repressor Proteins immunology, T-Box Domain Proteins genetics, T-Box Domain Proteins immunology, Th1 Cells metabolism, Cohesins, CD4-Positive T-Lymphocytes immunology, Interferon-gamma metabolism, Repressor Proteins metabolism, T-Box Domain Proteins metabolism, Th1 Cells immunology
Abstract

How cell type-specific differences in chromatin conformation are achieved and their contribution to gene expression are incompletely understood. Here we identify a cryptic upstream orchestrator of interferon-gamma (IFNG) transcription, which is embedded within the human IL26 gene, compromised of a single CCCTC-binding factor (CTCF) binding site and retained in all mammals, even surviving near-complete evolutionary deletion of the equivalent gene encoding IL-26 in rodents. CTCF and cohesins occupy this element in vivo in a cell type-nonspecific manner. This element is juxtaposed to two other sites located within the first intron and downstream of Ifng, where CTCF, cohesins, and the transcription factor T-bet bind in a T helper 1 (Th1) cell-specific manner. These interactions, close proximity of other elements within the locus to each other and to the gene encoding interferon-gamma, and robust murine Ifng expression are dependent on CTCF and T-bet. The results demonstrate that cooperation between architectural (CTCF) and transcriptional enhancing (T-bet) factors and the elements to which they bind is required for proper Th1 cell-specific expression of Ifng.

Published
2009
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