Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes
Copyright policy )Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes
Abstract The runt family transcription factors Runx1 and Runx3 are expressed in developing murine thymocytes. We show that enforced expression of full-length Runx1 in CD4−CD8− thymocytes results in a profound suppression of immature CD4/CD8 double-positive thymocytes and mature CD4 single-positive thymocytes compared with controls. This effect arises from Runx1- or Runx3-mediated repression of CD4 expression, and is independent of positively selecting signals. Runx1 is able to repress CD4 in CD4/CD8 double-positive thymocytes, but not in mature splenic T cells. Runx-mediated CD4 repression is independent of association with the corepressors Groucho/TLE or Sin3. Two domains are required for complete Runx-mediated CD4 repression. These are contained within Runx1 aa 212–262 and 263–360. The latter region contains the nuclear matrix targeting sequence, which is highly conserved among runt family transcription factors across species. The presence of the nuclear matrix targeting sequence is required for Runx-mediated CD4 repression, suggesting that Runx transcription factors are stabilized on the CD4 silencer via association with the nuclear matrix.
- California Institute of Technology United States
- University of Massachusetts Amherst United States
- University of Massachusetts System United States
- University of Toronto Canada
CD4-Positive T-Lymphocytes, Molecular Sequence Data, 610, Down-Regulation, Cell Differentiation, Mice, Transgenic, CD8-Positive T-Lymphocytes, Growth Inhibitors, Peptide Fragments, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Core Binding Factor Alpha 3 Subunit, Fetus, Organ Culture Techniques, Mice, Inbred DBA, CD4 Antigens, Core Binding Factor Alpha 2 Subunit, Animals, Nuclear Matrix, Amino Acid Sequence
CD4-Positive T-Lymphocytes, Molecular Sequence Data, 610, Down-Regulation, Cell Differentiation, Mice, Transgenic, CD8-Positive T-Lymphocytes, Growth Inhibitors, Peptide Fragments, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Core Binding Factor Alpha 3 Subunit, Fetus, Organ Culture Techniques, Mice, Inbred DBA, CD4 Antigens, Core Binding Factor Alpha 2 Subunit, Animals, Nuclear Matrix, Amino Acid Sequence
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).76 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!