The leukemia-associated ETO homologues are differently expressed during hematopoietic differentiation

Lindberg, Sofia Rondin; Olsson, André; Persson, Ann-Maj; Olsson, Inge

doi:10.1016/j.exphem.2004.10.011

Cited by 32 publications

(48 citation statements)

References 41 publications

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“…In human, ETO is expressed in CD34 þ cells, most hematopoietic tissues and various leukemic cell lines (Erickson et al, 1996;Fukuyama et al, 2001;Chevallier et al, 2004;Iban˜ez et al, 2004;Lindberg et al, 2005). In contrast, the pattern of ETO expression proved to be different in mice as ETO-deficient mice showed impaired development of the gastrointestinal system, but no hematopoietic defect was observed.…”

Section: Discussionmentioning

confidence: 99%

E2a/Pbx1 oncogene inhibits terminal differentiation but not myeloid potential of pro-T cells

Bourette

Mouchiroud

2006

Oncogene

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Section: Discussionmentioning

confidence: 99%

E2a/Pbx1 oncogene inhibits terminal differentiation but not myeloid potential of pro-T cells

Bourette

Mouchiroud

2006

Oncogene

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“…Based on our data, replacing full-length E proteins at target promoters with these variants should bypass the repression imposed by ETO corepressors, leading to constitutive activation of target promoters during a time frame when these variants are expressed at high levels. Indeed, it has been shown that HEBAlt is transiently upregulated in early T-cell precursors and plays a critical role in facilitating early T-cell development from hematopoietic stem cells (59), where various ETO corepressors are present at high levels (22,36,44,56).…”

Section: Discussionmentioning

confidence: 99%

“…The eight-twenty-one gene product ETO (also called MTG8) is a prototypical member of a small family of transcriptional corepressors that also includes ETO-2 and MTGR1 (MTG8-related protein 1) (29). ETO family proteins are expressed in a variety of cell types and tissues, including brain, intestine, and adipose tissues and the hematopoietic compartments (1,11,12,22,36,44,52,56). Like E proteins, members of this family of proteins (namely, ETO and ETO-2) are also targeted by oncogenic chromosomal translocations (27,29,34,46,49).…”

mentioning

confidence: 99%

Multivalent Binding of the ETO Corepressor to E Proteins Facilitates Dual Repression Controls Targeting Chromatin and the Basal Transcription Machinery

Guo

Yan

et al. 2009

Molecular and Cellular Biology

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E proteins are a family of helix-loop-helix transcription factors that play important roles in cell differentiation and homeostasis. They contain at least two activation domains, AD1 and AD2. ETO family proteins and the leukemogenic AML1-ETO fusion protein are corepressors of E proteins. It is thought that ETO represses E-protein activity by interacting with AD1, which competes away p300/CBP histone acetyltransferases. Here we report that E proteins contain another conserved ETO-interacting region, termed DES, and that differential associations with AD1 and DES allow ETO to repress transcription through both chromatin-dependent and chromatin-independent mechanisms. At the chromatin level, AD1 and AD2 cooperatively recruit p300. ETO interacts with AD1 to abolish p300 recruitment and to allow HDAC-dependent silencing. At the post-chromatin-remodeling level, binding to DES enables ETO to directly inhibit activation of the basal transcription machinery. This novel repression mechanism is conserved in ETO family proteins and in the AML1-ETO fusion protein. In addition, the repression capacity exerted by each mechanism is differentially modulated by cross talk among various ETO domains and the AML1 domain of AML1-ETO. In particular, the oligomerization domain of ETO plays a major role in targeting ETO to the DES region and independently potentiates the TAFH domain-mediated AD1 interaction. The ability to exert repression at different levels not only may allow these corepressors to impose robust inhibition of signal-independent transcription but may also allow a rapid response to signals. In addition, our newly defined domain interactions and their interplays have important implications in effectively targeting both E-protein fusion proteins and AML1-ETO found in cancers.

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“…Although ETO family members are widely expressed during embryogenesis and adult life (17,23), the pattern of their expression in hematopoiesis suggests a potential role in hematopoietic differentiation (43). In humans, ETO is detected in CD34 ϩ progenitor cells and up-regulated in erythroblasts (GPA ϩ CD71 ϩ cells) while ETO-2 (also called MTG16) is expressed at high levels in CD34 ϩ cells and downregulated during erythroid and granulocytic differentiation (43). In the mouse, ETO-2 is expressed in myeloid (FDCP-mix) and erythroid (MEL) cell lines (17).…”

Section: Discussionmentioning

confidence: 99%

ETO-2 Associates with SCL in Erythroid Cells and Megakaryocytes and Provides Repressor Functions in Erythropoiesis

Schuh

Tipping

Clark

et al. 2005

Molecular and Cellular Biology

134

205

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Lineage specification and cellular maturation require coordinated regulation of gene expression programs. In large part, this is dependent on the activator and repressor functions of protein complexes associated with tissue-specific transcriptional regulators. In this study, we have used a proteomic approach to characterize multiprotein complexes containing the key hematopoietic regulator SCL in erythroid and megakaryocytic cell lines. One of the novel SCL-interacting proteins identified in both cell types is the transcriptional corepressor ETO-2. Interaction between endogenous proteins was confirmed in primary cells. We then showed that SCL complexes are shared but also significantly differ in the two cell types. Importantly, SCL/ETO-2 interacts with another corepressor, Gfi-1b, in red cells but not megakaryocytes. The SCL/ETO-2/Gfi-1b association is lost during erythroid differentiation of primary fetal liver cells. Genetic studies of erythroid cells show that ETO-2 exerts a repressor effect on SCL target genes. We suggest that, through its association with SCL, ETO-2 represses gene expression in the early stages of erythroid differentiation and that alleviation/modulation of the repressive state is then required for expression of genes necessary for terminal erythroid maturation to proceed.

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The leukemia-associated ETO homologues are differently expressed during hematopoietic differentiation

Cited by 32 publications

References 41 publications

E2a/Pbx1 oncogene inhibits terminal differentiation but not myeloid potential of pro-T cells

E2a/Pbx1 oncogene inhibits terminal differentiation but not myeloid potential of pro-T cells

Multivalent Binding of the ETO Corepressor to E Proteins Facilitates Dual Repression Controls Targeting Chromatin and the Basal Transcription Machinery

ETO-2 Associates with SCL in Erythroid Cells and Megakaryocytes and Provides Repressor Functions in Erythropoiesis

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