Disclosed herein are methods and compositions useful for inhibiting interaction between a bromodomain protein and an immunoglobulin (Ig) regulatory element. The methods and compositions are particularly useful for downregulating expression of an oncogene translocated with an Ig locus, as well as for treating a cancer (e.g., hematological malignancy) characterized by increased expression of an oncogene which is translocated with an Ig locus. Also disclosed herein are methods and assays for identifying agents that interfere with binding of bromodomain proteins to Ig regulatory elements, as well as methods and assays for identifying inhibitors of bromodomain.