Two Distinct Transcription Factors that Bind the Immunoglobulin Enhancer μE5/κE2 Motif

Henthorn, Paula S.; Kiledjian, Megerditch; Kadesch, Tom

doi:10.1126/science.2105528

Cited by 461 publications

(340 citation statements)

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“…Functional studies indicate a positive regulatory role for E2A-HLF in gene expression, mediated through two separate domains (AD1 and AD2) in the E2A fusion element that act as potent trans-activators of gene expression in several contexts (12,13,(29)(30)(31). By contrast, NFIL3͞E4BP4 can function as either a trans-repressor or trans-activator of transcription in different cell types and promoter contexts (18)(19)(20).…”

Section: Resultsmentioning

confidence: 99%

Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes

Ikushima

Inukai

Inaba

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

131

142

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The E2A-HLF (hepatic leukemia factor) oncoprotein, generated in pro-B lymphocytes by fusion of the trans-activation domain of E2A to the basic region͞ leucine zipper (bZIP) domain of HLF, functions as an anti-apoptotic transcription factor in leukemic cell transformation. When introduced into interleukin 3 (IL-3)-dependent mouse pro-B lymphocytes, E2A-HLF prevents apoptosis induced by growth factor deprivation, suggesting that IL-3 mediates cell survival through activation of a transcription factor whose activity can be constitutively replaced by the chimeric oncoprotein. We considered four bZIP transcription factors as candidates for this putative IL-3-regulated factor, each of which binds avidly to the DNA consensus sequence recognized by E2A-HLF and is related to the Caenorhabditis elegans CES-2 (cell death specification protein) neuron-specific mediator of cell death. The expression and binding activity of the Nfil3 protein (also called E4bp4), but not of Hlf, Dbp, or Tef, was found to be regulated by IL-3 in mouse pro-B cell lines (Baf-3 and FL5.12). Northern blot analysis showed that Nfil3͞E4bp4 is regulated as a ''delayed-early'' IL-3-responsive gene, requiring de novo protein synthesis. In the absence of IL-3, enforced expression of the human NFIL3͞E4BP4 cDNA promoted the survival but not the growth of IL-3-dependent pro-B cells. Our results implicate NFIL3͞E4BP4 (nuclear factor regulated by IL-3͞adenovirus E4 promoter binding protein) in a distinct growth factor-regulated signaling pathway that is responsible for the survival of early B-cell progenitors, and whose alteration by E2A-HLF leads to childhood B lineage leukemia.

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Section: Resultsmentioning

confidence: 99%

Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes

Ikushima

Inukai

Inaba

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

131

142

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“…Members of the E2A family include E2-2, HEB and the products of the E2A gene E47 and E12 (Murre et al, 1989;Henthorn et al, 1990;Hu et al, 1992). Tal-1/E2A heterodimers preferentially recognize the E-box consensus sequence CAGATG (Hsu et al, 1994a) and exhibit transcriptional transactivation activity (Hsu et al, 1994c).…”

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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“…These clones were plaque purified, and the nucleotide sequence of a portion of each cDNA was determined (23). Analyses of these sequences revealed that one cDNA encoded the regulatory factor, E12 (26) and the other cDNA encoded the transcription factor, USF2 (14,25). Both E12 and USF2 have been shown to bind to E-box elements and to regulate the expression of a number of genes.…”

Section: Resultsmentioning

confidence: 99%

“…The human USF2a and USF2b expression cDNAs (25) and the mouse wild-type USF2a, mutant USF2a⌬N, and mutant TDUSF2a⌬B expression cDNAs (9) were generous gifts from Dr. Raymondjean and Dr. Sawadogo, respectively. The E12 expression vector was generously provided by Dr. Kadesch (26).…”

Section: Materials-mentioning

confidence: 99%

Regulation of the Nuclear Gene That Encodes the α-Subunit of the Mitochondrial F0F1-ATP Synthase Complex

Breen

Jordan

1997

Journal of Biological Chemistry

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We have previously identified several positive cis-acting regulatory regions in the promoters of the bovine and human nuclear-encoded mitochondrial F 0 F 1 -ATP synthase ␣-subunit genes (ATPA). One of these cis-acting regions contains the sequence 5 -CACGTG-3 (an Ebox), to which a number of transcription factors containing a basic helix-loop-helix motif can bind. This E-box element is required for maximum activity of the ATPA promoter in HeLa cells. The present study identifies the human transcription factor, upstream stimulatory factor 2 (USF2), as a nuclear factor that binds to the ATPA E-box and demonstrates that USF2 plays a critical role in the activation of the ATPA gene in vivo. Evidence includes the following. Antiserum directed against USF2 recognized factors present in HeLa nuclear extracts that interact with the ATPA promoter in mobility shift assays. Wild-type USF2 proteins synthesized from expression vectors trans-activated the ATPA promoter through the E-box, whereas truncated USF2 proteins devoid of the amino-terminal activation domains did not. Importantly, expression of a dominant-negative mutant of USF2 lacking the basic DNA binding domain but able to dimerize with endogenous USF proteins significantly reduced the level of activation of the ATPA promoter caused by ectopically coexpressed USF2, demonstrating the importance of endogenous USF2 in activation of the ATPA gene.Most cellular ATP is synthesized in the mitochondria through the process of oxidative phosphorylation. The mammalian mitochondrial oxidative phosphorylation system requires the functional interaction of gene products encoded by both the nuclear and the mitochondrial genomes (for reviews, see Refs. 1 and 2). The activities of the enzymes of the mammalian oxidative phosphorylation system vary greatly in response to a number of physiological conditions, including cell proliferation, hormonal stimulation, development, and differentiation (for reviews, see Refs. 3 and 4). The levels of these enzymes are controlled, at least in part, at a transcriptional level, although regulation at a post-transcriptional level also plays an important role in mitochondrial biogenesis (1-4).During the past several years, analysis of mammalian nuclear encoded oxidative phosphorylation genes has resulted in the identification of a number of regulatory factors that contribute to the transcription of these genes. Characterization of these gene regulatory mechanisms should allow the delineation of signals involved in the control of cellular energy production and, possibly, in the coordinate expression of genes encoding proteins of the oxidative phosphorylation system. Our laboratory has been analyzing the regulation of the nuclear gene that encodes the ␣-subunit of the mammalian mitochondrial F 0 F 1 -ATP synthase complex (ATPA) and has identified several positive cis-acting regulatory regions that are important for expression of this gene (5). Furthermore, we have found that protein factor(s) present in HeLa nuclei bind to these cis-acting regions. For e...

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Two Distinct Transcription Factors that Bind the Immunoglobulin Enhancer μE5/κE2 Motif

Cited by 461 publications

References 33 publications

Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes

Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes

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

Regulation of the Nuclear Gene That Encodes the α-Subunit of the Mitochondrial F0F1-ATP Synthase Complex

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