Methods and compositions for modulating gene expression

A method of decreasing expression of a gene within a cell, the gene being within an anchor sequence-mediated conjunction that comprises a first anchor sequence, a second anchor sequence, and an enhancer, the method comprising a step of:

• contacting the cell with a composition comprising a targeting element or a nucleic acid encoding the targeting element, wherein the targeting element comprises a Cas protein and gRNA which bind specifically to the first anchor sequence, the second anchor sequence, or both of the first anchor sequence and the second anchor sequence, relative to non-target anchor sequences within the cell with sufficient affinity that it competes with binding of CTCF within the cell, wherein the first and second anchor sequences each comprise a CTCF binding site wherein the CTCF binding site has the sequence of SEQ ID NO:
• 1 or SEQ ID NO:
• 2.