Helix‐loop‐helix transcription factors regulate Id2 gene promoter activity

Neuman, K.; Nornes, Howard O.; Neuman, Toomas

doi:10.1016/0014-5793(95)01128-2

Cited by 29 publications

(25 citation statements)

References 33 publications

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“…At the same time, expression of the LSD1 itself was not affected by atRA. Despite a slight increase in the b-catenin binding, combined treatment with Wnt3a and atRA had no readily detectable effect on LSD1 recruitment to the WRE, probably owing to sensitivity We were not able to identify in the Id2 gene promoter a DNA sequence resembling known RARE or RXRE, and no functional RARE was identified in the cloned Id2 promoter in earlier studies (Neuman et al, 1995). Nonetheless, we investigated whether RAR recruitment to the WRE at the Id2 promoter was entirely dependent on the binding of b-catenin.…”

Section: Resultsmentioning

confidence: 58%

“…Overexpression of another helix-loop-helix transcription factor NSCL was shown to abrogate RA-induced downregulation of Id2 in F9 cells (Neuman et al, 1995). The Id2 gene promoter harbors no DNA sequence, resembling known RAREs or RXREs (Neuman et al, 1995), and RAR binding to the Id2 WRE is b-catenin-dependent (Figure 5c) Thus, effects of atRA on the Id2 gene expression appear to be cell context-dependent and unlikely to be mediated by direct binding of the RARs to the gene promoter DNA.…”

Section: Discussionmentioning

confidence: 98%

“…In different cell systems, retinoids have been reported to downregulate (Neuman et al, 1995;Wagsater et al, 2003) and upregulate (Buzzard et al, 2003;Nigten et al, 2005) the Id2 gene expression. Overexpression of another helix-loop-helix transcription factor NSCL was shown to abrogate RA-induced downregulation of Id2 in F9 cells (Neuman et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

et al. 2007

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We investigated the effect of all-trans-retinoic acid (atRA) on proliferation in several human skin cell lines and found that antiproliferative potency of atRA correlated with the endogenous activity of canonical Wnt signaling. In HaCaT keratinocytes, we found that atRA significantly suppressed the expression of Id2, a member of the inhibitor of differentiation family of transcription factors that regulate cell growth and differentiation. However, no apparent change in the expression of other Wnt targets, like c-Myc or cyclin D1, was observed. Retinoid-induced Id2 gene suppression was associated with decreased levels of histone H3 and H4 acetylation and histone H3 Lys-4 methylation, and with recruitment of the LSD1 demethylase at the Wnt-response element (WRE) (TCF/LEF-binding site), in the Id2 gene promoter. None of such changes was detected at the WRE of c-Myc and cyclin D1 gene promoters. Inhibition of Id2 by short interfering RNA (siRNA) had a similar effect on the proliferation of HaCaT cells as exposure to atRA, whereas anti-b-catenin siRNA significantly inhibited its antiproliferative effect. These data suggest that downregulation of Id2 gene expression through transcriptional convergence between Wnt and retinoid signaling pathways underlies the antiproliferative effect of retinoids in keratinocytes, and provide evidence of gene-targeted crosstalk between signaling pathways.

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Section: Resultsmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

et al. 2007

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Section: Discussionmentioning

confidence: 99%

“…ID2 proteins dimerize with other bHLH proteins, thereby inhibiting their DNA-binding activities (39). E-box sequences in the Id2 promoter are potential regulatory targets for circadian bHLH-PAS transcription factors (39). In a recent microarray analysis of SCN and liver, Id2 provided a prototype for a large cluster of circadianregulated genes (24).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Peripheral Circadian Clocks in Adipose Tissues

et al. 2006

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Helix-loop-helix proteins in Schwann cells: A study of regulation and subcellular localization of Ids, REB, and E12/47 during embryonic and postnatal development

et al. 1997

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Although basic helix-loop-helix (bHLH) proteins play an important role in transcriptional control in many cell types, the role of HLH proteins in Schwann cells has yet to be assessed. In this study, we have analyzed the expression of the dominant negative HLH genes, Id1 to Id4 and the class A gene REB, during Schwann cell development. We found that mRNA derived from these genes was present in the Schwann cell lineage throughout development including embryonic precursors and mature cells. The mRNA levels were not significantly regulated during development. Nevertheless, by using antibodies against the four different Id proteins, we found clear regulation of some of these genes at the protein level, in particular Id 2, 4, and REB, both in amount and nuclear/cytoplasmic localization. All these proteins are found in the nuclei of Schwann cell precursors but are not seen in nuclei of Schwann cells of newborn nerves. We observed extensive overlap in Id expression, especially in Schwann cell precursors that co-expressed all four Id proteins and REB. We also showed that Id 1 and 2 were up-regulated as Schwann cells progressed through the cell cycle. These data indicate that HLH transcription factors act as regulators of Schwann cell development and point to the existence of as yet unidentified cell type-specific bHLH proteins in these cells.

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Helix‐loop‐helix transcription factors regulate Id2 gene promoter activity

Cited by 29 publications

References 33 publications

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

Characterization of Peripheral Circadian Clocks in Adipose Tissues

Helix-loop-helix proteins in Schwann cells: A study of regulation and subcellular localization of Ids, REB, and E12/47 during embryonic and postnatal development

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