Ikaros represses CD38 through interaction with the NuRD complex. (A) Coimmunoprecipitation performed in OPM2 cells with anti-CHD4 (CHD4-IP) antibody or mouse-immunoglobulin G (Mock-IP) control. Membranes were probed for Ikaros. MW are shown on the left. Positions of the Ikaros and IgH proteins are indicated. (B) Analysis of Ikaros, MTA2, and MTA3 binding in the human B-cell line GM12878 by ChIP-seq from the ENCODE Project. Shown are the mapping track of sequence reads in each library at the CD38 locus. Ikaros conservatively called peaks are shown as bars in the top panel. (C) Histogram of CD38 expression by flow cytometry in OPM2 cells 48 hours after treatment with Len 1 μM and/or panobinostat (Pano) 10 nM or untreated control. (D) Graph of CD38 MFI in OPM2 cells 48 hours after treatment with Len 1 μM and/or Pano 10 nM and/or β-IFN (50 IU). Data are the MFI ± SD from 3 experiments. ****P < .0001, ***P < .001, **P < .01, *P < .05, using an unpaired Student t test. (E) Cartoon of model suggested: Transcriptional activation of ISGs, including CD38, results from signal transduction after the binding of interferon (α or β) to the type 1 interferon receptor, activation of JAK1, STAT1/2, and together with IRF9, assembly of the ISGF3 complex, which translocates to the nucleus and binds to IFN-stimulated response elements. Expression of ISGs is normally repressed to an extent by Ikaros and Aiolos, likely through interaction with the NuRD complex. Hence, CD38 expression can be augmented through treatment with IFN, IMiDs including lenalidomide and histone deacetylase inhibitors such as panobinostat.