Hydroxyl radical footprinting protocol

 

1. Wipe test: Using small circular paper, wipe inside box (1), plastic tray (2), outside yellow vial (3), and inside yellow vial (4). Put each paper into scintialliation vial labeled 1-4 and count with scintillation counter in Shearn lab. Use program 9, user 1. Counts should be <25 cpm. Record (1), (2), and (4) on radiation form.

 

2. Label oligos:

(1) 8 bp 5Õ + nic + 40 bp 3Õ (.033 nmol/ml)              10mM: 1.5 ml .033 nmol/ml + 3.5 ml dH20

(2) 24 bp 5Õ + nic + 24 bp 3Õ (.036 nmol/ml)                        10mM: 1.4 ml .036 nmol/ml + 3.6 ml dH20

(3) 40 bp 5Õ + nic + 8 bp 3Õ (.026 nmol/ml)              10mM: 1.9ml .026 nmol/ml + 3.1 ml dH20

(c1) R&C 24 bp 5Õ + nic + 24 bp 3Õ (.017 nmol/ml) 10mM: 2.9 ml .017 nmol/ml + 2.1 ml dH20

(c2) PamÕs TraY OriT (.017 nmol/ml)                       10mM: 2.9 ml .017 nmol/ml + 2.1 ml dH20

 

Prepare the following reaction:

 

 

Incubate @ 37¡C 45 min

Incubate @ 70¡C 10 min

Cool briefly, spin briefly

+ 30 ml sterile dH20

+ 50 ml phenol: chloroform: isoamyl alcohol

Vortex, spin 2 min

Prepare Spin column

Invert column several times to resuspend

Sit column over collection tube

Spin @ 2200 rpm 1 min

Discard flowthru and place column in new tube

Apply aqueous layer over spin column and spin 2 min @ 2200 rpm

1:50 dilution

Read counts of 2 ml of 1:50 dilution

 

3. Prepare the following buffer to a total volume of 50 ml:

 

 

4. To 1ml of the above buffer, add 1 mg/ml calf DNA.

 

5. Prepare the following solutions to a total volume of 50ml:

            DNA in H20

            DNA in 0 nM TraI36

            DNA in 100 nm TraI36

 

 

TraI36 dilution: 88.96mM initial concentration

100nM: 3.4ml (8.896mM TraI36)+ 296.6ml (buffer + calf DNA) = 300 ml

0 nM: 300ml buffer + calf DNA = 300 ml

 

6. Incubate 50, 000 cpm oligos with TraI36 for 1.5 hours @ RT. (3:30-5 pm)

 

 

DNA (ml)

1:50 dilution

Protein

 

 

TraI36 (88.96mM)

Buffer + calf DNA

H2O

Oligo 1 in H20

3.5

0

0

46.5

Oligo 1 in 0 nM TraI36

3.5

0

46.5

0

Oligo 1 in 1000 nM TraI36

3.5

46.5

0

0

 

 

 

 

 

Oligo 2 in H20

8.2

0

0

41.8

Oligo 2 in 0 nM TraI36

8.2

0

41.8

0

Oligo 2 in 1000 nM TraI36

8.2

41.8

0

0

 

 

 

 

 

Oligo 3 in H20

1.8

0

0

48.2

Oligo 3 in 0 nM TraI36

1.8

0

48.2

0

Oligo 3 in 1000 nM TraI36

1.8

48.2

0

0

 

 

 

 

 

Oligo C(1) in H20

7.5

0

0

42.5

Oligo C(1) in 0nM TraI36

7.5

0

42.5

0

Oligo C(1) in 1000 nM TraI36

7.5

42.5

0

0

 

 

 

 

 

Oligo C(2) in H20

16

0

0

34

Oligo C(2) in 0nM TraI36

16

0

34

0

Oligo C(2) in 1000 nM TraI36

16

34

0

0

 

7. Add to cap of tube:

 

            2 ml (125 mM Fe (II) + 250 mM EDTA)

            2 ml 28 mM NaAscorbate

            2 ml 0.8% H202

 

Close tube and spin down solutions.

 

8. Incubate 2 min @  RT.

 

9. Stop rxn by adding 150 ml stop solution to each tube.

 

1 sample                               15 + 1 samples

112 ml TE                               1792 ml TE   

10 ml 0.1M thiourea             160 ml 0.1M thiourea

25 ml 3M NaAc                      400 ml 3M NaAc

2 ml 0.2M EDTA                    32 ml 0.2M EDTA

5 ml 1 mg/ml tRNA   80 ml 1 mg/ml tRNA

 

9. Extract w/ phenol chloroform

Add equal volume of bottom layer of phenol: chloroform

Vortex

Spin 2 min @ max speed

Take off top layer

Repeat 1x

 

10. Ethanol precipitate

+ 10% 3M NaAc (.1 x 200=20ml)

+ 2.5x 95% EtOH (2.5 x 200=500ml)

Sit @ -80¡C > 15 min

Spin max speed @ 4¡C 15 min

Wash w/  20 ml 70% EtOH

Sit @ -20¡C 5 min

Spin max @ 4¡C 8 min

Aspirate 70% EtOH

Speed vac 15 min

Dissolve in 5ml TE + 5ml formamide loading buffer.

 

11. Read counts.

 

12. Prepare 12% sequencing gel with thin spacers and 20-well comb.

 

50 ml 12% sequencing gel

 

24 ml SequaGel concentrate

21 ml SequaGel diluent

5 ml SequaGel buffer

400 ml 10% APS

20 ml TEMED

 

Rinse wells with 1xTBE.

Pre-run gel at 300 V 30 min.

Load 3ml sample/lane. Load G-reaction of each labeled oligo.

Run at 300-500 V 2h.

 

13. Soak gel with bottom glass plate in 10% MeOH + 10% acetic acid 45 min.

 

14. Dry gel 1h 15 min. Expose overnight in phosphoimager casette.

 

15. Develop 16 hours later in Schleif lab.