p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

Huang, Suming; Qiu, Yi; Stein, Roland; Brandt, Stephen J.

doi:10.1038/sj.onc.1202889

Cited by 81 publications

(90 citation statements)

References 87 publications

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“…Both CBP and its close relative p300 function to either activate or suppress the activity of many transcription factors including p53, p73, cJun, ATF-2, GATA1, SCL and EKLF, among others (Avantaggiati et al, 1997;Lee et al, 1996;Blobel et al, 1998;Blobel, 2000;Zeng et al, 2000;Huang et al, 1999;Hung et al, 1999). However, it is not known whether, in erythroid cells CPB or p300 interact with any of the forkhead transcription factors to regulate their activity.…”

Section: Introductionmentioning

confidence: 96%

Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells

et al. 2002

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The mammalian forkhead transcription factors, FOXO3a (FKHRL1), FOXO1a (FKHR) and FOXO4 (AFX) are negatively regulated by PKB/Akt kinase. In the present study we examined the engagement of forkhead family of transcription factors in erythropoietin (Epo)-and stem cell factor (SCF)-mediated signal transduction. Our data show that all three forkhead family members, FOXO3a, FOXO1a and FOXO4 are phosphorylated in human primary erythroid progenitors. Experiments performed to determine various upstream signaling pathways contributing to phosphorylation of forkhead family members show that only PI-3-kinase pathway is required for inactivation of FOXO3a. Our data also demonstrate that during Epo deprivation FOXO3a interacts with the transcriptional coactivator p300 and such interaction is disrupted by stimulation of cells with Epo. To determine the domains in FOXO3a, mediating its interaction with p300, we performed GST pull-down assays and found that the Nterminus region containing the ®rst 52 amino acids was su cient for binding p300. Finally, our data demonstrate that FOXO3a and FOXO1a are acetylated during growth factor deprivation and such acetylation is reversed by stimulation with Epo. Thus mammalian forkhead transcription factors are involved in Epo and SCF signaling in primary erythroid progenitors and may play a role in the induction of apoptotic and mitogenic signals.

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Section: Introductionmentioning

confidence: 96%

Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells

et al. 2002

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“…However, under physiologic conditions where inhibitory HLH Id proteins are expressed, tal-1/ E2A heterodimer is a signi®cantly better transcriptional activator than the E2A homodimer (Voronova and Lee, 1994). In addition, tal-1 has been shown to interact with both transcriptional co-repressors and co-activators (Wadman et al, 1994;Huang et al, 1999;. Thus, tal-1-induced leukemogenesis may re¯ect the aberrant activation of novel target genes or alternatively, sequestration of E2A proteins and alteration of E2A-target genes.…”

Section: Introductionmentioning

confidence: 99%

The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice

et al. 2001

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Activation of the basic helix ± loop ± helix (bHLH) gene TAL-1 (or SCL) is the most frequent gain-of-function mutation in pediatric T cell acute lymphoblastic leukemia (T-ALL). Similarly, mis-expression of tal-1 in the thymus of transgenic mice results in the development of clonal T cell lymphoblastic leukemia. To determine the mechanism(s) of tal-1-induced leukemogenesis, we created transgenic mice expressing a DNA binding mutant of tal-1. Surprisingly, these mice develop disease, demonstrating that the DNA binding properties of tal-1 are not required to induce leukemia/lymphoma in mice. However, wild type tal-1 and the DNA binding mutant both form stable complexes with E2A proteins. In addition, tal-1 stimulates di erentiation of CD8-single positive thymocytes but inhibits the development of CD4-single positive cells: e ects also observed in E2A-de®cient mice. Our study suggests that the bHLH protein tal-1 contributes to leukemia by interfering with E2A protein function(s). Oncogene (2001) 20, 3897 ± 3905.

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“…42,50 The regions of transcription factor binding colocalize with chromatin that is DNase I hypersensitive and enriched for acetylated H3/H4 only in hematopoietic cells. As both GATA1 and SCL associate with histone acetyltransferases (HATs), 51,52 it is likely that they recruit HAT activity and that this, at least in part, results in the enrichment of histone acetylation that is detected. …”

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confidence: 99%

Differences in the chromatin structure and cis-element organization of the human and mouse GATA1 loci: implications for cis-element identification

Valverde-Garduño

Guyot

Anguita

et al. 2004

Blood

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Cis-element identification is a prerequisite to understand transcriptional regulation of gene loci. From analysis of a limited number of conserved gene loci, sequence comparison has proved a robust and efficient way to locate ciselements. Human and mouse GATA1 genes encode a critical hematopoietic transcription factor conserved in expression and function. Proper control of GATA1 transcription is critical in regulating myeloid lineage specification and maturation. Here, we compared sequence and systematically mapped position of DNase I hypersensitive sites, acetylation status of histone H3/H4, and in vivo binding of transcription factors over approximately 120 kilobases flanking the human GATA1 gene and the corresponding region in mice. Despite lying in approximately 10 megabase (Mb) conserved syntenic segment, the chromatin structures of the 2 homologous loci are strikingly different. The 2 previously unidentified hematopoietic cis-elements, one in each species, are not conserved in position and sequence and have enhancer activity in erythroid cells. In vivo, they both bind the transcription factors GATA1, SCL, LMO2, and Ldb1. More broadly, there are both species-and regulatory elementspecific patterns of transcription factor binding. These findings suggest that some cis-elements regulating human and mouse GATA1 genes differ. More generally, mouse human sequence comparison may fail to identify all cis-elements. IntroductionGATA1 is a key hematopoietic transcription factor and a member of a conserved family of GATA factors that execute a program of differentiation in diverse cell types. 1 The precise pattern of GATA1 expression is critical for its function. Gain-of-function experiments demonstrate that GATA1 directs cell fate of myeloid progenitors in a manner dependent on the level of GATA1 expressed and that GATA1 expression has to be extinguished to allow neutrophil and macrophage differentiation. [2][3][4] Loss-of-function experiments show that GATA1 is required for terminal maturation of erythroid cells, megakaryocytes, eosinophils, and mast cells. [5][6][7][8] Moreover, reduction of GATA1 levels to 20% of normal is insufficient for erythroid maturation. 9 Lastly, rescue experiments in GATA1-mutant hematopoietic cells 10 and mice 11 and analysis of knock-in mice 12 show that GATA1 function is determined not just by specific GATA1 protein sequences (other GATA factors can, to a large extent, replace GATA1), but is also critically dependent on the precise pattern of GATA1 expression.Consistent with this function, in both human and mouse definitive hematopoiesis, GATA1 expression is detected at a low level in the common myeloid progenitor (CMP) 13,14 and is selectively maintained in erythroid cells, megakaryocytes, eosinophils, and mast cells (reviewed in Orkin 15 ) and repressed in neutrophils and monocytes. 4 Outside blood cells, GATA1 is expressed in testis where its role is unclear. Taken together, these observations argue that the time, place (cell-type), and level of GATA1 expression help regulate output...

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p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

Cited by 81 publications

References 87 publications

Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells

Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells

The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice

Differences in the chromatin structure and cis-element organization of the human and mouse GATA1 loci: implications for cis-element identification

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