Human high mobility group box transcription factor 1 affects thymocyte development and transgene variegation.
It has been shown previously that a human CD2 (hCD2) disabled locus control region (LCR) transgene is unable to establish an open chromatin configuration in all the T cells, and this leads to position effect variegation of the transgene. In this study we show that thymus-specific overexpression of human high mobility group box transcription factor 1 (HBP1), a transcription factor that binds a specific sequence within the hCD2 LCR, affects thymus cellularity as well as the number of CD8(+) thymocytes in two independent transgenic mouse lines and increases the proportion of T cells that fully activate the transgenic locus in hCD2 variegating mice in a sequence-specific dependent manner. This finding suggests that overexpression of HBP1 can affect lineage commitment and can relieve the suppressive influence of heterochromatin, allowing thymocytes to express the variegating target locus more efficiently. These effects could be the result of direct HBP1 action on LCR activity. Alternatively, the extra HBP1 molecules may sequester repressive elements away from the LCR, thus allowing transcription permissive states to form on the transgene locus.
Sekkali
Belaïd
B
National Institute for Medical Research, Division of Molecular Immunology, London, United Kingdom.
Szabat
Ewa
E
Ktistaki
Eleni
E
Tolaini
Mauro
M
Roderick
Kathleen
K
Harker
Nicky
N
Patel
Amisha
A
Williams
Keith
K
Norton
Trisha
T
Kioussis
Dimitris
D
D000818:Animals; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D019076:Transgenes
D018801:CD2 Antigens; D006131:Growth Inhibitors; C486328:HBP1 protein, human; D006609:High Mobility Group Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)