Methods and compositions for modulating gene expression

A chimeric protein, comprising:

• a targeting element comprising a sequence targeting polypeptide that binds in or around an anchor sequence associated with a target anchor sequence-mediated conjunction;
• and
• an effector domain comprising all or a biologically active portion of an epigenetic modifying agent, wherein the chimeric protein modifies the anchor sequence associated with the target anchor sequence-mediated conjunction, wherein the target anchor sequence-mediated conjunction is not located in a promoter;
• wherein the anchor sequence comprises a CTCF binding site;
• wherein the anchor sequence is associated with a nucleotide repeat;
• and wherein the nucleotide repeat is associated with a disease, wherein the disease is chosen from Huntington's Disease, DRPLA (Dentatorubropallidoluysian atrophy), SBMA (Spinal and bulbar muscular atrophy), SCA1 (Spinocerebellar ataxia Type 1), SCA2 (Spinocerebellar ataxia Type 2), SCA3 (Spinocerebellar ataxia Type 3), SCA6 (Spinocerebellar ataxia Type 6), SCAT (Spinocerebellar ataxia Type 7), SCA17 (Spinocerebellar ataxia Type 17), FRDA (Friedreich's ataxia), DM (Myotonic dystrophy), SCA8 (Spinocerebellar ataxia Type 8) or SCA12 (Spinocerebellar ataxia Type 12).