A novel Snail-related transcription factor Smuc regulates basic helix-loop-helix transcription factor activities via specific E-box motifs

Kataoka, Hiroshi; Murayama, Toshinori; Yokode, Masayuki; Mori, Seiichi; Sano, Hideto; Ozaki, H.; Yokota, Yoshifumi; Nishikawa, Shin‐Ichi; Kita, Toru

doi:10.1093/nar/28.2.626

Cited by 80 publications

(101 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the conserved N-terminal eight amino acids that hScrt shares with other SNAG domain containing proteins are not required for repressor function. This observation is in contrast to other reports ascribing important repressor function to the N-terminal twenty amino acids of the SNAG domain of vertebrate Snail, Slug, Smuc, and Gfi1 proteins (8,13,14,24). Though modest nuclear targeting activity has been described for this N-terminal region of Gfi1, effective nuclear localization depends on the full-length protein, including the zinc finger domain (14).…”

Section: Discussioncontrasting

confidence: 96%

“…Because the Snail consensus binding sequence contains the E-box motif CAGGTG recognized by bHLH transcription factors (22) and functional interactions between Snail and bHLH proteins have been reported (13,23), we tested the ability of hASH1 to bind to the same sequence. When either hASH1 or E12, a heterodimerizing partner for bHLH proteins, was used alone, no or only a modest shift of the wild-type Snail probe was seen, respectively (data not shown).…”

Section: Specific Expression Of Hscratch In Lung Cancers With Ne Featmentioning

confidence: 99%

“…Vertebrate Slug appears to regulate cell migration (10,11) and exhibits antiapoptotic activity in pro-B cells (12). Mouse Smuc is expressed in muscle and thymus and may influence muscle differentiation (13). All vertebrate Snail family members are C 2 H 2 -type zinc finger transcription factors that possess an N-terminal SNAG domain that is not present in invertebrates.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mammalian Scratch: A neural-specific Snail family transcriptional repressor

Nakakura

Watkins

Schuebel

et al. 2001

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

View full text Add to dashboard Cite

Members of the Snail family of zinc finger transcription factors are known to play critical roles in neurogenesis in invertebrates, but none of these factors has been linked to vertebrate neuronal differentiation. We report the isolation of a gene encoding a mammalian Snail family member that is restricted to the nervous system. Human and murine Scratch (Scrt) share 81% and 69% identity to Drosophila Scrt and the Caenorhabditis elegans neuronal antiapoptotic protein, CES-1, respectively, across the five zinc finger domain. Expression of mammalian Scrt is predominantly confined to the brain and spinal cord, appearing in newly differentiating, postmitotic neurons and persisting into postnatal life. Additional expression is seen in the retina and, significantly, in neuroendocrine (NE) cells of the lung. In a parallel fashion, we detect hScrt expression in lung cancers with NE features, especially small cell lung cancer. hScrt shares the capacity of other Snail family members to bind to E-box enhancer motifs, which are targets of basic helix-loop-helix (bHLH) transcription factors. We show that hScrt directly antagonizes the function of heterodimers of the proneural bHLH protein achaete-scute homolog-1 and E12, leading to active transcriptional repression at E-box motifs. Thus, Scrt has the potential to function in newly differentiating, postmitotic neurons and in cancers with NE features by modulating the action of bHLH transcription factors critical for neuronal differentiation.

show abstract

Section: Discussioncontrasting

confidence: 96%

Section: Specific Expression Of Hscratch In Lung Cancers With Ne Featmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mammalian Scratch: A neural-specific Snail family transcriptional repressor

Nakakura

Watkins

Schuebel

et al. 2001

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

View full text Add to dashboard Cite

show abstract

“…This is further suggested by observations indicating that Snail family members repress the expression of tissuespecific inducers as the pro-neural genes sim and rho 29 and the skeletal muscle master regulator MyoD. 30 …”

Section: Discussionmentioning

confidence: 82%

An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs

et al. 2011

View full text Add to dashboard Cite

Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular minicircuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene HNF4a, directly represses the expression of the epithelial microRNAs (miRs)-200c and -34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4a, previously identified as a transcriptional repressor of Cellular differentiation implies an orchestrated sequence of events guiding stem cells/precursors toward specialized cell types based on the contemporary and strictly correlated phenomena of loss of stemness and acquisition of histotypic markers and functions. The homeostasis of the stem cell compartment requires mechanisms actively counteracting differentiation; 1 similarly, the maintenance of the differentiated state involves a stable repression of elements capable to induce morphological transition and dedifferentiation. 2 The observation that a number of stem cells are restricted to a specific differentiation fate suggests that elements pivotal for the coordinated execution of the opposite processes could be tissue-specific. Considering that stem cell compartments are rare and give rise to a heterogeneous cellular population capable to reversibly shift among different states, 3 the availability of a stable stem cell line executing specific differentiation programs discloses an unique possibility to investigate mechanisms regulating alternative cellular choices. A simple and direct molecular mini-circuitry of master elements of mutually exclusive biological processes, also able to reciprocally influence their own expression, may provide the theoretically best device to trigger such complex phenomena.We previously characterized a number of stable liver stem cell lines named RLSCs (from resident liver stem cells) that spontaneously acquire an epithelial morphology and differentiate into hepatocytes (named RLSCdH from RLSC-derived hepatocytes). Notably, RLSCs were also proved to recapitulate the hepatocyte post-differentiation patterning defined as 'zonation': their spontaneous differentiation, in fact, generates periportal hepatocytes that may be induced to switch into perivenular hepatocytes by means of the convergence of Wnt signaling on the HNF4a-driven transcription. 4 Furthermore, we identified a simple cross-regulatory circuitry between HNF4a (master regulator of hepatocyte differentiation) and Snail (master regulator of the epithelial-to-mesenchymal transition, EMT), whose expression is mutually exclusive because of their direct reciprocal transcriptional repression. 2,5 These findings, relevant for the comprehension of the EMT and of the reverse process mesenchymal-...

show abstract

“…15 and 27). Mouse Snail family members include Snail (Sna), Slug (Slugh), and Smuc (28). Expression patterns of mouse Snail and Slug in the early developmental stage suggest involvement of Snail and Slug in chondrogenesis (24, 28 -30).…”

mentioning

confidence: 99%

Mouse Snail Family Transcription Repressors Regulate Chondrocyte, Extracellular Matrix, Type II Collagen, and Aggrecan

Seki

Fujimori

Savagner

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Snail family genes are conserved among species during evolution and encode transcription factors expressed at different stages of development in different tissues. These genes are involved in a broad spectrum of biological functions: cell differentiation, cell motility, cell cycle regulation, and apoptosis. However, little is known about the target genes involved in these functions. Here we show that mouse Snail family members, Snail (Sna) and Slug (Slugh), are involved in chondrocyte differentiation by controlling the expression of type II collagen (Col2a1) and aggrecan. In situ hybridization analysis of developing mouse limb demonstrated that Snail and Slug mRNAs were highly expressed in hypertrophic chondrocytes. Inversely, the expression of collagen type II mRNA disappeared during hypertrophic differentiation. Snail and Slug mRNA expression was down-regulated during differentiation of the mouse chondrogenic cell line ATDC5 and overexpression of exogenous Snail or Slug in ATDC5 cells inhibited expression of collagen type II and aggrecan mRNA. Reporter analysis revealed Snail and Slug suppressed the promoter activity of Col2a1, and the E-boxes in the promoter region were the responsible element. Gel shift assay demonstrated the binding of Snail to the E-box. Because type II collagen and aggrecan are major functional components of extracellular matrix in cartilage, these results suggest an important role for Snailrelated transcription repressors during chondrocyte differentiation.During skeletal development, condensed mesenchymal cells give rise to chondrocytes and form cartilage primordia, which serve as templates for endochondral bone formation. In cartilage primordia, chondrocytes undergo further differentiation, starting as proliferating chondrocytes, becoming prehypertrophic chondrocytes and ending as hypertrophic chondrocytes. Chondrocytes secrete abundant extracellular matrix (ECM) 1 into the extracellular space, and the composition of ECM changes during the sequential differentiation steps. Type II collagen and aggrecan are major components of the cartilage extracellular matrix produced by proliferating and prehypertrophic chondrocytes, and type X collagen is a major collagen type produced by hypertrophic chondrocytes. The differentiation into hypertrophic chondrocytes is accompanied with changes in ECM; switching of collagen types from type II to type X and the disappearance of aggrecan and link protein (1, 2

show abstract

A novel Snail-related transcription factor Smuc regulates basic helix-loop-helix transcription factor activities via specific E-box motifs

Cited by 80 publications

References 44 publications

Mammalian Scratch: A neural-specific Snail family transcriptional repressor

Mammalian Scratch: A neural-specific Snail family transcriptional repressor

An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs

Mouse Snail Family Transcription Repressors Regulate Chondrocyte, Extracellular Matrix, Type II Collagen, and Aggrecan

Contact Info

Product

Resources

About