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result sql = Engineering zinc finger protein transcription factors to downregulate the epithelial glycoprotein-2 promoter as a novel anti-cancer treatment.
Engineering zinc finger protein transcription factors to downregulate the epithelial glycoprotein-2 promoter as a novel anti-cancer treatment.
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char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = -;code = 45
char = T;code = 84
char = F;code = 70
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = .;code = 46
char = ;code = 32
char = U;code = 85
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = g;code = 103
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 3;code = 51
char = -;code = 45
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 9;code = 57
char = ;code = 32
char = b;code = 98
char = p;code = 112
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = 3;code = 51
char = -;code = 45
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = -;code = 45
char = T;code = 84
char = F;code = 70
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 6;code = 54
char = 0;code = 48
char = %;code = 37
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = o;code = 111
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = %;code = 37
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = -;code = 45
char = T;code = 84
char = F;code = 70
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = -;code = 45
char = T;code = 84
char = F;code = 70
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = v;code = 118
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = -;code = 45
char = T;code = 84
char = F;code = 70
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = -;code = 45
char = d;code = 100
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = G;code = 71
char = P;code = 80
char = -;code = 45
char = 2;code = 50
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = Z;code = 90
char = F;code = 70
char = P;code = 80
char = -;code = 45
char = T;code = 84
char = F;code = 70
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Zinc finger protein transcription factors (ZFP-TFs) are emerging as powerful novel tools for the treatment of many different diseases. ZFPs are DNA-binding motifs and consist of modular zinc finger domains. Each domain can be engineered to recognize a specific DNA triplet, and stitching six domains together results in the recognition of a gene-specific sequence. Inhibition of gene expression can be achieved by fusing a repressor domain to these DNA-binding motifs. In this study, we engineered ZFP-TFs to downregulate the activity of the epithelial glycoprotein-2 (EGP-2) promoter. The protein EGP-2 is overexpressed in a wide variety of cancer types and EGP-2 downregulation has been shown to result in a decreased oncogenic potential of tumor cells. Therefore, downregulation of EGP-2 expression by ZFP-TFs provides a novel anti-cancer therapeutic. Using a straightforward strategy, we engineered a 3-ZFP that could bind a 9 bp sequence within the EGP-2 promoter. After the addition of a repressor domain, this 3-ZFP-TF could efficiently downregulate EGP-2 promoter activity by 60%. To demonstrate the flexibility of this technology, we coupled an activation domain to the engineered ZFP, resulting in a nearly 200% increase in EGP-2 promoter activity. To inhibit the endogenous EGP-2 promoter, we engineered 6-ZFP-TFs. Although none of the constructed ZFP-TFs could convincingly modulate the endogenous promoter, efficient and specific inhibition of the exogenous promoter was observed. Overall, ZFP-TFs are versatile bi-directional modulators of gene expression and downregulation of EGP-2 promoter activity using ZFP-TFs can ultimately result in a novel anti-cancer treatment.

Publication: Mol. Carcinog. 2007 May ;46(5)::391-401.
Publication Date: 2007 May
Study Author(s): Gommans, Willemijn M;McLaughlin, Pamela M J;Lindhout, Beatrice I;Segal, David J;Wiegman, D J;Haisma, Hidde J;van der Zaal, Bert J;Rots, Marianne G;
Institution: Department of Therapeutic Gene Modulation, University of Groningen, Groningen, The Netherlands.
Shortcut link to this study:
Zinc finger protein transcription factors (ZFP-TFs) are emerging as powerful novel tools for the treatment of many different diseases. ZFPs are DNA-binding motifs and consist of modular zinc finger domains. Each domain can be engineered to recognize a specific DNA triplet, and stitching six domains together results in the recognition of a gene-specific sequence. Inhibition of gene expression can be achieved by fusing a repressor domain to these DNA-binding motifs. In this study, we engineered ZFP-TFs to downregulate the activity of the epithelial glycoprotein-2 (EGP-2) promoter. The protein EGP-2 is overexpressed in a wide variety of cancer types and EGP-2 downregulation has been shown to result in a decreased oncogenic potential of tumor cells. Therefore, downregulation of EGP-2 expression by ZFP-TFs provides a novel anti-cancer therapeutic. Using a straightforward strategy, we engineered a 3-ZFP that could bind a 9 bp sequence within the EGP-2 promoter. After the addition of a repressor domain, this 3-ZFP-TF could efficiently downregulate EGP-2 promoter activity by 60%. To demonstrate the flexibility of this technology, we coupled an activation domain to the engineered ZFP, resulting in a nearly 200% increase in EGP-2 promoter activity. To inhibit the endogenous EGP-2 promoter, we engineered 6-ZFP-TFs. Although none of the constructed ZFP-TFs could convincingly modulate the endogenous promoter, efficient and specific inhibition of the exogenous promoter was observed. Overall, ZFP-TFs are versatile bi-directional modulators of gene expression and downregulation of EGP-2 promoter activity using ZFP-TFs can ultimately result in a novel anti-cancer treatment.
PMID: 17186549

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