STANDARD_NAME	RIZ_ERYTHROID_DIFFERENTIATION_APOBEC2
SYSTEMATIC_NAME	M15638
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RIZ_ERYTHROID_DIFFERENTIATION_APOBEC2
NAMESPACE	AFFY_MG_U74
DESCRIPTION_BRIEF	Selected genes whose expression profile follows that of APOBEC2 [GeneID=10930] 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 5S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	100301_at,101059_at,101704_at,102235_at,102580_r_at,102716_at,103050_at,103761_at,104494_at,104506_at,104592_i_at,160615_at,161798_r_at,92334_at,92445_at,92469_at,92726_at,92753_at,92990_at,93075_r_at,94203_at,96507_at,96994_at,97159_at,97745_at,98821_at,99900_at
GENE_SYMBOLS	ESRRB,NDN,HNF4G,MYCL,HOXA6,EYA3,TCF21,TFCP2L1,SOWAHC,NR1I3,MEF2C,PIAS3,,,CACNA1A,SFRP4,SOX6,MEIS3,ZNF235,NFATC2,LCOR,EVX2,HIC1,AIRE,HOXA4,PDX1,CRX
FOUNDER_NAMES