Promoter‐specific regulation of gene expression by an exogenously added homeodomain that promotes neurite growth

Roux, Isabelle; Duharcourt, Sandra; Volovitch, Michel; Prochiantz, Alain; Ronchi, Elettra

doi:10.1016/0014-5793(95)00681-x

Cited by 23 publications

(18 citation statements)

References 7 publications

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“…Luciferase activity was measured 24 hours after transfection (Le Roux et al, 1995) in a Lumat luminometer (Berthold). Results presented are the mean of three independent experiments.…”

Section: Pull-down Interaction Assaymentioning

confidence: 99%

Joint regulation of the MAP1B promoter by HNF3β/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors

et al. 2003

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The MAP1B (Mtap1b) promoter presents two evolutionary conserved overlapping homeoproteins and Hepatocyte nuclear factor 3β (HNF3β/Foxa2) cognate binding sites (defining putative homeoprotein/Fox sites, HF1 and HF2). Accordingly, the promoter domain containing HF1 and HF2 is recognized by cerebellum nuclear extracts containing Engrailed and Foxa2 and has regulatory functions in primary cultures of embryonic mesmetencephalic nerve cells. Transfection experiments further demonstrate that Engrailed and Foxa2 interact physiologically in a dose-dependent manner: Foxa2 antagonizes the Engrailed-driven regulation of the MAP1B promoter, and vice versa. This led us to investigate if Engrailed and Foxa2 interact directly. Direct interaction was confirmed by pull-down experiments, and the regions participating in this interaction were identified. In Foxa2 the interacting domain is the Forkhead box DNA-binding domain. In Engrailed, two independent interacting domains exist: the homeodomain and a region that includes the Pbx-binding domain. Finally, Foxa2 not only binds Engrailed but also Lim1, Gsc and Hoxa5 homeoproteins and in the four cases Foxa2 binds at least the homeodomain. Based on the involvement of conserved domains in both classes of proteins, it is proposed that the interaction between Forkhead box transcription factors and homeoproteins is a general phenomenon.

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“…Luciferase activity was measured 24 hours after transfection (Le Roux et al, 1995) in a Lumat luminometer (Berthold). Results presented are the mean of three independent experiments.…”

Section: Pull-down Interaction Assaymentioning

confidence: 99%

Joint regulation of the MAP1B promoter by HNF3β/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors

et al. 2003

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“…Frequency and nuclear localization of transfected homeoproteins were verified by immunocytochemistry with anti-myc 9E10 antibody (Evan et al, 1985). L uciferase activity was measured 24 hr after transfection (Le Roux et al, 1995) in a L umat luminometer (Berthold, Bald Wilbald, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…This was shown by the use of the homeodomain of Antennapedia (AntpHD) and by its mutated version where glutamine in position 50 has been replaced by an alanine (AntpHD-50A). Indeed, AntpHD-50A is internalized and conveyed to the nucleus but does not bind DNA with high affinity (Le and, contrary to AntpHD, does not regulate gene expression (Le Roux et al, 1995;Mainguy et al, 1999).…”

Section: Technologymentioning

confidence: 99%

“…Indeed, En1 gain of function in the chick embryo rostral tectum provokes an abnormal transcription of the two genes at the site of En1 overexpression (Logan et al, 1996). Several homeodomains are internalized by cells in culture (for review, see Prochiantz, 2000) and conveyed to their nucleus, where they specifically interfere with transcription (Le Roux et al, 1995). This property has been exploited to antagonize the binding of endogenous homeoproteins to their cognate promoters in physiological conditions.…”

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confidence: 99%

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The NeuronalMicrotubule-Associated Protein 1BIs under Homeoprotein Transcriptional Control

et al. 2001

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To identify genes regulated by homeoprotein transcription factors in postnatal neurons, the DNA-binding domain (homeodomain) of Engrailed homeoprotein was internalized into rat cerebellum neurons. The internalized homeodomain (EnHD) acts as a competitive inhibitor of Engrailed and of several homeoproteins (Mainguy et al., 2000). Analysis by differential display revealed that microtubule-associated protein 1B (MAP1B) mRNA is upregulated by EnHD. This upregulation does not require protein synthesis, suggesting a direct effect of the homeodomain on MAP1B transcription. The promoter region of MAP1B was cut into several subdomains, and each subdomain was tested for its ability to bind Engrailed and EnHD and to associate with Engrailed-containing cerebellum nuclear extracts. In addition, the activity, and regulation by Engrailed, of each subdomain and of the entire promoter were evaluated in vivo by electroporation in the chick embryo neural tube. These experiments demonstrate that MAP1B promoter is regulated by Engrailed in vivo. Moreover, they show that one promoter domain that contains all ATTA homeoprotein cognate binding sites common to the rat and human genes is an essential element of this regulation. It is thus proposed that MAP1B, a cytoskeleton protein involved in neuronal growth and regeneration, is under homeoprotein transcriptional regulation. Key words: neuronal morphogenesis; cytoskeleton; MAP1B; transcriptional targets; homeoproteins; engrailed; in vivo electroporation; differential displayHomeoproteins are homeogene-coded transcription factors. They are characterized by a highly conserved 60-amino acid DNAbinding domain, the homeodomain (Gehring et al., 1994), and play key roles at all developmental stages. In the mouse, Engrailed homeogene expression starts at the one-and five-somite stages for Engrailed1 (En1) and Engrailed2 (En2), respectively. In the brain, Engrailed transcripts are localized to the mid-hindbrain region, and although En2 is expressed later than En1, both genes show identical transcription patterns at the eight-somite stage (Davidson et al

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“…Recently, a series of virus-encoded and other regulatory proteins were found to possess the ability to cross biological membranes. For example, peptides derived from the Drosophila Antennapedia homeodomain are internalized by cells in culture (1,2) and conveyed to cell nuclei where they can directly and specifically interfere with transcription (2,3). The HIV-1 Tat protein was reported to enhance intercellular trafficking in vitro (4,5).…”

mentioning

confidence: 99%

Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors

Lai

Han

Zirzow

et al. 2000

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

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Promoter‐specific regulation of gene expression by an exogenously added homeodomain that promotes neurite growth

Cited by 23 publications

References 7 publications

Joint regulation of the MAP1B promoter by HNF3β/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors

Joint regulation of the MAP1B promoter by HNF3β/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors

The NeuronalMicrotubule-Associated Protein 1BIs under Homeoprotein Transcriptional Control

Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors

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