Chromosome conformation analysis

1. A method of determining the three-dimensional arrangement of the chromatin within a cell, comprising:

a) isolating cells from a biological sample;

b) incubating the cells with a cross-linking agent, thereby cross-linking proteins with DNA and forming a cross-linked product;

c) lysing the cells;

d) digesting the DNA with a restriction endonuclease;

e) incubating the digested DNA with a phosphatase;

f) ligating a first looped half-adaptor to the digested DNA thereby forming a first ligation product and a second looped half-adaptor to the digested DNA thereby forming a second ligation product, wherein the first and second looped half-adaptors are different from each other and each looped half-adaptor comprises a stem-loop structure complementary to the stem-loop structure of the other half-adaptor, wherein the 5′ end of the stem of each looped half-adaptor comprises a 5′-overhang that terminates in a 5′-phosphate group and is ligated to the digested DNA;

g) heating the first and second ligation products thereby allowing the half-adaptors to anneal to each other;

h) treating the product of step g) with a kinase and a ligase to ligate the looped half-adaptors to the digested DNA thereby forming a third ligation product; and

i) analyzing the third ligation product.

2. The method according to claim 1 , wherein the analyzing step is performed using the polymerase chain reaction (PCR).

3. The method according to claim 1 , further comprising the step of incubating the cross-linked product with a cross-linking quencher.

4. The method according to claim 1 , wherein the lysing step comprises incubating the cells with one or more detergents.

5. The method according to claim 4 , wherein the one or more detergents are selected from the group consisting of anionic detergents and non-ionic detergents.

6. The method according to claim 1 , wherein the cross-linking agent comprises formaldehyde.