Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes

• Published in: The Journal of immunology (1950) Vol. 172; no. 7; pp. 4359 - 4370
• Main Authors: Telfer, Janice C, Hedblom, Emmett E, Anderson, Michele K, Laurent, Micheline N, Rothenberg, Ellen V
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.2004
• Subjects: Amino Acid Sequence; Animals; CD4 Antigens - biosynthesis; CD4 Antigens - metabolism; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - physiology; Core Binding Factor Alpha 2 Subunit; Core Binding Factor Alpha 3 Subunit; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Down-Regulation - immunology; Fetus; Growth Inhibitors - biosynthesis; Growth Inhibitors - metabolism; Growth Inhibitors - physiology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Molecular Sequence Data; Nuclear Matrix - physiology; Organ Culture Techniques; Peptide Fragments - physiology; Protein Isoforms - biosynthesis; Protein Isoforms - metabolism; Protein Isoforms - physiology; Protein Structure, Tertiary; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - physiology; Repressor Proteins - biosynthesis; Repressor Proteins - metabolism; Repressor Proteins - physiology; Sequence Deletion; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism; Transcription Factors - biosynthesis; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.7.4359

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.