Human HMG box transcription factor HBP1: a role in hCD2 LCR function.
The locus control region (LCR) of the human CD2 gene (hCD2) confers T cell-specific, copy-dependent and position-independent gene expression in transgenic mice. This LCR consists of a strong T cell-specific enhancer and an element without enhancer activity (designated HSS3), which is required for prevention of position effect variegation (PEV) in transgenic mice. Here, we identified the HMG box containing protein-1 (HBP1) as a factor binding to HSS3 of the hCD2 LCR. Within the LCR, HBP1 binds to a novel TTCATTCATTCA sequence that is higher in affinity than other recently reported HBP1-binding sites. Mice transgenic for a hCD2 LCR construct carrying a deletion of the HBP1-binding sequences show a propensity for PEV if the transgene integrates in a heterochromatic region of the chromosome such as the centromere or telomere. We propose that HBP1 plays an important role in chromatin opening and remodelling activities by binding to and bending the DNA, thus allowing DNA-protein and/or protein-protein interactions, which increase the probability of establishing an active locus.
Zhuma
T
T
Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Tyrrell
R
R
Sekkali
B
B
Skavdis
G
G
Saveliev
A
A
Tolaini
M
M
Roderick
K
K
Norton
T
T
Smerdon
S
S
Sedgwick
S
S
Festenstein
R
R
Kioussis
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics*; D003001:Cloning, Molecular; D016172:DNA Fingerprinting; D003850:Deoxyribonuclease I; D004926:Escherichia coli / Q000235:genetics; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015183:Restriction Mapping; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology
D018801:CD2 Antigens; C486328:HBP1 protein, human; C486329:Hbp1 protein, mouse; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D003850:Deoxyribonuclease I