Modulation of enhancer rna mediated gene expression

Abstract

Disclosed herein are methods and compounds for inhibiting gene expression by inhibiting enhancer RNAs (eRNAs). Such methods and compounds are useful for reducing expression of certain genes, many of which are associated with a variety of diseases and disorders.

1 . A method of inhibiting expression of a gene in a cell comprising contacting the cell with a specific inhibitor of an enhancer RNA (eRNA), and thereby inhibiting expression of the gene in the cell; wherein the specific inhibitor is an antisense compound comprising a modified oligonucleotide complementary to the eRNA. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the cell is mammalian. 
     
     
         4 . The method of  claim 1 , wherein transcription of the eRNA is initiated from a RNA polymerase II (PolII) binding site and is capable of elongating bidirectionally. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the eRNA is transcribed from a genomic enhancer sequence or region having a higher level of monomethylated lysine 4 of histone 3 (H3K4me1) than trimethylated lysine 4 of histone 3 (H3K4me3). 
     
     
         7 - 14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the eRNA enhances transcription of chemokine receptor CX3CR1. 
     
     
         16 . The method  claim 1 , wherein the transcriptional start site of the one or more genes is located on a chromosome at least 1 kilobase (kb) from the genomic enhancer sequence or region. 
     
     
         17 . (canceled) 
     
     
         18 . The method  claim 3 , wherein the cell is a hematopoietic cell. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 18 , wherein the hematopoietic cell is a macrophage. 
     
     
         21 . The method of  claim 1 , wherein the cell is a neuron. 
     
     
         22 . The method of  claim 1 , wherein the cell is a breast cell. 
     
     
         23 . The method of  claim 1 , wherein the cell is a cancer cell. 
     
     
         24 . The method of  claim 1 , wherein the cell contacted with a specific inhibitor of an enhancer RNA (eRNA) is in a subject. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 1 , wherein the antisense compound is single-stranded. 
     
     
         27 . The method of  claim 1 , wherein the antisense compound is double-stranded. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 29 , wherein the modified oligonucleotide is 12 to 30 nucleosides in length. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 1 , wherein the modified oligonucleotide comprises at least one modified sugar. 
     
     
         33 . The method of  claim 32 , wherein the at least one modified sugar is a bicyclic sugar. 
     
     
         34 . The method of  claim 32 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl group. 
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 1 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage. 
     
     
         37 - 87 . (canceled)