Molecular Characterization of the Novel Basic Helix–Loop–Helix Protein DEC1 Expressed in Differentiated Human Embryo Chondrocytes

Shen, Ming; Kawamoto, Takeshi; Yan, Weiqun; Nakamasu, Kazuko; Tamagami, M.; Koyano, Yasuhiko; Noshiro, Mitsuhide; Kato, Yukio

doi:10.1006/bbrc.1997.6960

Cited by 144 publications

(154 citation statements)

References 28 publications

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“…Based on sequence alignment and functional domain analyses, human DEC proteins, along with mouse STRA and rat SHARP, constitute a new class of bHLH transcription factors (7)(8)(9)(10). These proteins are shown to play important roles in cell differentiation, regulation of molecular clock, immune response, and xenobiotic response (7, 10, 19 -22, 28).…”

Section: Discussionmentioning

confidence: 99%

“…The HLH domain in the bHLH motif is responsible for dimerization, whereas the basic region mediates DNA binding (1). Based on sequence alignment and domain analysis, human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) constitute a new and structurally distinct class of bHLH proteins (7)(8)(9)(10). These proteins are distantly related to Drosophila Hairy and E(spl) as well as the mammalian homologues (e.g.…”

mentioning

confidence: 99%

“…They exhibit an overlapping tissue distribution, and their expression is highly elevated in response to environmental stimuli (7)(8)(9)(10). In rats that undergo seizure induction by kainic acid, the levels of mRNA encoding SHARP1 or -2 are sharply increased within 1 h in the brain (9).…”

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confidence: 99%

“…In addition to a potential protective role against environmental stimuli, DEC/STRA/SHARPs have been implicated in cell differentiation (7,10,20), maturation of lymphocytes (21), and regulation of molecular clock (22). In a cell culture system, mouse STRA13 promotes neuronal but represses mesodermal and endodermal differentiation (7).…”

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DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

Xie

Song

et al. 2003

Journal of Biological Chemistry

125

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Human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) proteins constitute a new and structurally distinct class of the basic helix-loop-helix proteins. In each species, two members are identified with a sequence identity of >90% in the basic helix-loop-helix region and ϳ40% in the total proteins, respectively. Recently, we have reported that DEC1 is abundantly expressed in colon carcinomas but not in the adjacent normal tissues. The present study was undertaken to extend the expression study of DEC1 and to determine whether DEC1 and DEC2 had similar expression patterns among paired cancer-normal tissues from the colon, lung, and kidney. Without exceptions, DEC1 was markedly higher in the carcinomas, whereas the opposite was true with DEC2. In stable transfectants, tetracycline-induced expression of DEC1 caused proportional decreases in the expression of DEC2. Co-transfection with DEC1 repressed the activity of a DEC2 promoter reporter by as much as 90%. The repression was observed with wild type DEC1 but not its DNA binding-defective mutants. Studies with deletion and site-directed mutants located, in the proximal promoter, an E-box motif that supported the DEC1-mediated repression. Disruption of this E-box markedly abolished the ability of the reporter to respond to DEC1. Our findings assign for DEC1 the first target gene that is regulated through direct DNA binding. DEC/STRA/ SHARP proteins are highly identical in the DNA binding domain but much more diverse in other areas. DEC1-mediated repression on the expression of DEC2 provides an important mechanism that these transcription factors regulate the cellular function not only by modulating the expression of their target genes but also the expression of members within the same class.The basic helix-loop-helix (bHLH) 1 proteins are intimately associated with developmental events such as cell differentiation and lineage commitment (1-6). The HLH domain in the bHLH motif is responsible for dimerization, whereas the basic region mediates DNA binding (1). Based on sequence alignment and domain analysis, human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) constitute a new and structurally distinct class of bHLH proteins (7-10). These proteins are distantly related to Drosophila Hairy and E(spl) as well as the mammalian homologues (e.g. HES) with the highest sequence identity (ϳ40%) in the bHLH region (1,11,12). Like Hairy/E(spl)/Hes, DEC/STRA/SHARPs contain an orange domain and a proline residue in the DNA binding domain. However, the proline is located 2 residues more toward the NH 2 terminus (1, 8). Another major structural difference on the functional domains is that DEC/STRA/ SHARPs, unlike Hairy/E(Spl)/Hes proteins, lack the COOHterminal WRPW tetrapeptide motif (13). Through this sequence, Hairy/E(spl)/Hes recruit corepressor Groucho to the transcription regulatory complex (13)....

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Section: Discussionmentioning

confidence: 99%

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DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

Xie

Song

et al. 2003

Journal of Biological Chemistry

125

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“…Its expression is increased in response to DNA damaging agents, di erentiation signals and growth inhibitory drugs (Bates et al, 1996;Horne et al, 1997). DEC1/Stra13 (Shen et al, 1997), is a transcriptional repressor whose expression is associated with induction of growth arrest and terminal di erentiation (Boudjelal et al, 1997;Sun and Taneja, 2000). Furthermore, in addition to its role in matrix cross linking, increased expression of transglutaminase 2 characterizes cells undergoing apoptosis, and inhibition protects against several apoptotic stimuli (Oliverio et al, 1999 and references within).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

et al. 2000

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The von Hippel-Lindau tumour suppressor gene (VHL) targets hypoxia inducible factor (HIF)-a subunits for ubiquitin dependent proteolysis. To better understand the role of this and other putative pathways of gene regulation in VHL function we subjected mRNA from VHL defective renal carcinoma cells and transfectants re-expressing a wild type VHL allele to di erential expression pro®ling, and analysed VHL target genes for oxygen regulated expression. Among a group of newly identi®ed VHL target genes the majority but not all were regulated by oxygen, indicating that whilst dysregulation of the HIF system makes a dominant contribution to alterations in transcription, VHL has other in¯uences on patterns of gene expression. Genes newly de®ned as targets of the VHL/hypoxia pathway (conditionally downregulated by VHL in normoxic cells) include aminopeptidase A, collagen type V, alpha 1, cyclin G2, DEC1/Stra13, endothelin 1, low density lipoprotein receptor-related protein 1, MIC2/CD99, and transglutaminase 2. These genes have a variety of functions relevant to tumour biology. However, not all are connected with the promotion of tumour growth, some being pro-apoptotic or growth inhibitory. We postulate that co-ordinate regulation as part of the HIF pathway may explain this paradox, and that evolution of antiapoptotic pathways may be required for tumour growth under VHL-dysregulation. Our results indicate that it will be necessary to consider the e ects of abnormal activity in integral regulatory pathways, as well as the e ects of individual genes to understand the role of abnormal patterns of gene expression in cancer. Oncogene (2000) 19, 6297 ± 6305.

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Isolation, identification and differentiation of human embryonic cartilage stem cells

Yan

et al. 2015

Cell Biology International

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We isolated human embryonic cartilage stem cells (hECSCs), a novel stem cell population, from the articular cartilage of eight-week-old human embryos. These stem cells demonstrated a marker expression pattern and differentiation potential intermediate to those of human embryonic stem cells (hESCs) and human adult stem cells (hASCs). hECSCs expressed markers associated with both hESCs (OCT4, NANOG, SOX2, SSEA-3 and SSEA-4) and human adult stem cells (hASCs) (CD29, CD44, CD90, CD73 and CD10). These cells also differentiated into adipocytes, osteoblasts, chondrocytes, neurons and islet-like cells under specific inducing conditions. We identified N(6), 2'-O-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP) as an inducer of chondrogenic differentiation in hECSCs. Similar results using N(6), 2'-O-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP) were obtained for two other types of human embryonic tissue-derived stem cells, human embryonic hepatic stem cells (hEHSCs) and human embryonic amniotic fluid stem cells (hEASCs), both of which exhibited a marker expression pattern similar to that of hECSCs. The isolation of hECSCs and the discovery that N(6), 2'-O-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP) induces chondrogenic differentiation in different stem cell populations might aid the development of strategies in tissue engineering and cartilage repair.

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Molecular Characterization of the Novel Basic Helix–Loop–Helix Protein DEC1 Expressed in Differentiated Human Embryo Chondrocytes

Cited by 144 publications

References 28 publications

DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling

Isolation, identification and differentiation of human embryonic cartilage stem cells

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