UNASSIGNED: In @entity1582 ( @entity1582 ) @entity690 rarely heal because of persistent suppressed osteoblast differentiation resulting in a high fracture risk. Herein, chromatin immunoprecipitation analyses reveal that @entity1582 cells induce repressive epigenetic histone changes at the @entity8087 locus that prevent osteoblast differentiation. The most pronounced @entity1582 -induced changes were at the @entity8087 -P1 promoter, converting it from a poised bivalent state to a repressed state. Previously it was observed that @entity1582 induce the transcription repressor @entity29476 in osteoblast precursors, which correlates with decreased @entity8087 expression. Thus, prompting detailed characterization of the @entity1582 and @entity310 -dependent @entity29476 -response element within the @entity8087 -P1 promoter. Further analyses reveal that @entity1582 -induced @entity29476 binding to @entity8087 in osteoblast precursors and recruitment of the histone modifiers @entity17029 , @entity34860 , and @entity16719 is required to establish and maintain @entity8087 repression in osteogenic conditions. These @entity29476 -mediated repressive chromatin changes persist even after removal of @entity1582 . Ectopic @entity29476 is sufficient to bind to @entity8087 , recruit @entity17029 and @entity16719 , increase H3K27me3 on the gene, and prevent osteogenic induction of endogenous @entity8087 expression. @entity29476 knockdown in MC4 cells blocked @entity1582 -induced recruitment of @entity17029 and @entity16719 to @entity8087 , acquisition of repressive chromatin architecture, and suppression of OB differentiation. Importantly, inhibition of @entity16719 or @entity17029 activity in pre-osteoblasts after @entity1582 exposure in vitro or in osteoblast precursors from @entity1582 @entity1 reversed the repressive chromatin architecture at @entity8087 and rescued osteoblast differentiation. IMPLICATIONS: This study suggests that therapeutically targeting @entity16719 or @entity17029 activity may reverse the profound @entity1582 -induced osteoblast suppression and allow repair of the @entity75 .

@entity16719 or XXXX Inhibition Reverses Multiple Myeloma-Induced Epigenetic Suppression of Osteoblast Differentiation.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity8087 :: ('860', 'Gene') :: ['Runx2'] @entity29476 :: ('2672', 'Gene') :: ['Gfi1', 'GFI1'] @entity310 :: ('7124', 'Gene') :: ['TNFa'] @entity16719 :: ('2146', 'Gene') :: ['EZH2'] @entity75 :: ('MESH:D001927', 'Disease') :: ['lytic lesions'] @entity34860 :: ('23028', 'Gene') :: ['LSD1'] @entity1582 :: ('MESH:D009101', 'Disease') :: ['multiple myeloma', 'MM'] @entity690 :: ('MESH:D030981', 'Disease') :: ['osteolytic lesions'] @entity17029 :: ('3065', 'Gene') :: ['HDAC1']
@entity17029 :: (3065,Gene) :: ['HDAC1']
