The human CD6 gene is transcriptionally regulated by RUNX and Ets transcription factors in T cells.
CD6 is a lymphocyte surface receptor involved in lymphocyte activation and differentiation processes that is constitutively expressed on developing and mature T cells and on the B1a cells. To define the molecular basis for the tissue-specific expression of CD6 we have identified the transcription factors that control the activity of the proximal regulatory region of the human CD6 gene. The TATA-less CD6 promoter contains multiple transcriptional start sites, and its preferential activity in human T lymphocytes is dependent on RUNX- and Ets-binding sites located within a highly conserved region. RUNX and Ets-1 factors transactivated the CD6 promoter through recognition of the -215 and -230 binding sites, respectively. Chromatin immunoprecipitation assays revealed that RUNX1 constitutively occupies the CD6 promoter in vivo, and knockdown experiments demonstrated that the steady-state level of CD6 mRNA is dependent on the expression of RUNX1, RUNX3 and Ets-1 transcription factors. Therefore, RUNX1/3 and Ets1 control the expression of CD6 in human T lymphocytes, thus expanding the range of T-cell specific and developmentally regulated lymphocyte gene targets involved in T-cell activation and differentiation.
Arman
Mònica
M
Servei d'Immunologia, Hospital Clínic Universitari de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Facultat de Medicina, Universitat de Barcelona, Villarroel 170, 08036 Barcelona, Spain.
Aguilera-Montilla
Noemí
N
Mas
Virgínia
V
Puig-Kröger
Amaya
A
Pignatelli
Miguel
M
Guigó
Roderic
R
Corbí
Angel-Luis
AL
Lozano
Francisco
F
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000502:physiology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; C493728:RUNX1 protein, human; C493729:Runx3 protein, human