STANDARD_NAME RIZ_ERYTHROID_DIFFERENTIATION_CCNE1 SYSTEMATIC_NAME M11048 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RIZ_ERYTHROID_DIFFERENTIATION_CCNE1 NAMESPACE AFFY_MG_U74 DESCRIPTION_BRIEF Selected gradually up-regulated genes whose expression profile follows that of CCNE1 [GeneID=898] in the TLX1 [GeneID=3195] Tet On iEBHX15-4 cells (pro-erythroblasts). DESCRIPTION_FULL Aberrant expression of the human homeobox-containing proto-oncogene TLX1/HOX11 inhibits hematopoietic differentiation programs in a number of murine model systems. Here, we report the establishment of a murine erythroid progenitor cell line, iEBHX1S-4, developmentally arrested by regulatable TLX1 expression. Extinction of TLX1 expression released the iEBHX1S-4 differentiation block, allowing erythropoietin-dependent acquisition of erythroid markers and hemoglobin synthesis. Coordinated activation of erythroid transcriptional networks integrated by the acetyltransferase co-activator CREB-binding protein (CBP) was suggested by bioinformatic analysis of the upstream regulatory regions of several conditionally induced iEBHX1S-4 gene sets. In accord with this notion, CBP-associated acetylation of GATA-1, an essential regulator of erythroid differentiation, increased concomitantly with TLX1 downregulation. Coimmunoprecipitation experiments and glutathione-S-transferase pull-down assays revealed that TLX1 directly binds to CBP, and confocal laser microscopy demonstrated that the two proteins partially colocalize at intranuclear sites in iEBHX1S-4 cells. Notably, the distribution of CBP in conditionally blocked iEBHX1S-4 cells partially overlapped with chromatin marked by a repressive histone methylation pattern, and downregulation of TLX1 coincided with exit of CBP from these heterochromatic regions. Thus, we propose that TLX1-mediated differentiation arrest may be achieved in part through a mechanism that involves redirection of CBP and/or its sequestration in repressive chromatin domains. PMID 17213805 GEOID AUTHORS Riz I,Akimov SS,Eaker SS,Baxter KK,Lee HJ,Mariño-Ramírez L,Landsman D,Hawley TS,Hawley RG CONTRIBUTOR Leona Saunders CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 2S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 100050_at,100452_at,100461_at,100616_at,100941_at,100984_at,101382_at,101475_at,101589_at,101888_at,101930_at,101958_f_at,101959_r_at,102242_at,102654_at,102819_at,102963_at,103285_at,103546_at,103598_at,104220_at,92235_g_at,92244_at,92468_at,93089_at,93129_at,93250_r_at,93708_at,94031_at,94521_at,95791_s_at,95795_at,96050_at,96084_at,96192_at,97327_at,97789_at,97965_at,98002_at,98032_at,98038_at,98469_at,98981_s_at,99486_at,99587_at,99932_at GENE_SYMBOLS ID1,KLF1,POLR2J,CENPA,PIAS2,ATF1,PBX2,BMI1,HMGN2,,NFIX,TFDP1,TFDP1,PER3,GATA1,NAP1L2,E2F1,MBD4,FOSL2,DHX9,SMAD6,RXRA,EXO1,ANKRD49,EIF4A2,CUX2,HMGB2,PIAS3,RAB2A,CDKN2D,SRSF2,SUPT4H1,SMARCB1,HNRNPDL,SP3,FEN1,FOXH1,PLA2G6,IRF8,,HMGB3,AURKB,TCF12,CENPB,RAB7A,ZBTB17 FOUNDER_NAMES