Negative regulation of CD4 gene expression by a HES-1-c-Myb complex.
Expression of the CD4 gene is tightly controlled throughout thymopoiesis. The downregulation of CD4 gene expression in CD4(-) CD8(-) and CD4(-) CD8(+) T lymphocytes is controlled by a transcriptional silencer located in the first intron of the CD4 locus. Here, we determine that the c-Myb transcription factor binds to a functional site in the CD4 silencer. As c-Myb is also required for CD4 promoter function, these data indicate that depending on the context, c-Myb plays both positive and negative roles in the control of CD4 gene expression. Interestingly, a second CD4 silencer-binding factor, HES-1, binds to c-Myb in vivo and induces it to become a transcriptional repressor. We propose that the recruitment of HES-1 and c-Myb to the silencer leads to the formation of a multifactor complex that induces silencer function and repression of CD4 gene expression.
Allen
R D
RD
Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Kim
H K
HK
Sarafova
S D
SD
Siu
G
G
D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D015704:CD4 Antigens / Q000235:genetics*; D002460:Cell Line; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D016296:Mutagenesis; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D015704:CD4 Antigens; D018985:Epitopes, B-Lymphocyte; D018398:Homeodomain Proteins; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human