STANDARD_NAME	RIZ_ERYTHROID_DIFFERENTIATION_HEMGN
SYSTEMATIC_NAME	MM510
COLLECTION	M2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/mouse/geneset/RIZ_ERYTHROID_DIFFERENTIATION_HEMGN
NAMESPACE	AFFY_MG_U74
DESCRIPTION_BRIEF	Selected gradually up-regulated genes whose expression profile follows that of HEMGN [GeneID=55363] 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 4S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	101305_at,101310_at,102643_at,102715_at,102882_at,103204_r_at,103229_at,103990_at,104292_at,104408_s_at,160109_at,161340_r_at,161521_at,161858_f_at,161965_r_at,162016_f_at,92249_g_at,92342_at,92697_at,92705_at,92781_at,92926_at,92933_at,92935_at,93616_g_at,97123_at,97704_at,97777_at,97937_at,98073_at,99527_at
GENE_SYMBOLS	Pou3f3,Tal2,Hoxa2,Nr2f1,Zfp46,E2f8,Ncoa1,Fosb,Eya2,Sox18,Sox4,,,,,,Nr4a2,Sox1,Foxa1,Tbx2,Tmpo,Mpl,Pou2f3,Runx1t1,Pbx3,Nr0b2,Ell2,Nkx2-5,Klf5,Cux1,Nfe2l3
FOUNDER_NAMES