The Broad Institute, Inc.

Baylor College of Medicine

Harvard College

Suhas Rao

Eric Lander

Erez Lieberman Aiden

Elena Stamenova

Olga Dudchenko

Miriam Huntley

Andrew Jewett

Su-Chen Huang

Erez Lieberman-Aiden

Adrian L Sanborn

Neva C Durand

Disclosed are methods for detecting spatial proximity relationships between nucleic acid sequences in a cell. The methods include: providing a sample of one or more cells comprising nucleic acids; fragmenting the nucleic acids present in the cells, wherein the fragmented nucleic acids have ends capable of joining to other fragmented nucleic acids; joining ends of fragmented nucleic acids to other ends fragmented nucleic acid to create at least one nucleic acid concatemer having at least one junction between the joined fragmented nucleic acids, and wherein the at least one nucleic acid concatemer encodes the information about the proximity of the DNA sequences in the cell; and determining the sequence at least one junction of the at least one nucleic acid concatemer, thereby detecting spatial proximity relationships between nucleic acid sequences in a cell.

Methods of determining multiple interactions between nucleic acids in a cell

Disclosed is an in situ method for detecting spatial proximity relationships between nucleic acid sequences, such as DNA, in a cell. The method includes: providing a sample of one or more cells comprising nucleic acids; fragmenting the nucleic acids present in the cells that leaves 5' overhanging ends; filling in the overhanging ends with at least one labeled nucleotide; joining the filled in end of the fragmented nucleic acids that are in close physical proximity to create one or more end joined nucleic acid fragments having a junction; isolating the one or more end joined nucleic acid fragments using the labeled nucleotide; and determining the sequence at the junction of the one or more end joined nucleic acid fragments.

Method for in situ determination of nucleic acid proximity

Chromatin 3D structure modulating agents in the context of the present invention are intended to interfere or manipulate the function of loop anchor motifs, such as CTCF motifs. In certain example embodiments, the present invention may block formation of an loop anchor or chromatin domain or induce formation of a loop anchor or chromatin domain at a targeted genomic location. For instance, a loop anchor motif can be altered, such as by mutating (including inverting) a binding motif so as to remove such a motif, or by adding new binding motifs in new locations within a loop domain, so as to reduce the size of an existing loop, so as to modify the size of an existing loop, or combinations thereof. Alternatively, the chromatin 3D structure modulating agent may bind a target region and mask a loop anchor motif, thereby preventing a loop anchor or chromatin domain from forming. The chromatin 3D structure modulating agent may bind a target region and cause a loop anchor of chromatin domain to form.

Methods and compositions for altering function and structure of chromatin loops and/or domains

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Medfield, MA, United States of America

Suhas Rao