δEF1 and SIP1 are differentially expressed and have overlapping activities during Xenopus embryogenesis

The zinc finger/homeodomain transcription factor (zfhx1) family in vertebrates consists of two members, δEF1 and SIP1. They have been proposed to display antagonistic activities in the interpretation of Smad‐dependent TGFβ signaling during mesoderm formation. We cloned Xenopus δEF1 cDNA, analyzed the expression profile of the gene, and compared the inducing and interacting properties of the protein to that of XSIP1. Whereas XSIP1 RNA is selectively expressed in the early developing nervous system, we show that XδEF1 gene transcription is only activated during neurulation and that its expression is restricted to the paraxial mesoderm. From early tail bud stage, XδEF1 and XSIP1 are coexpressed in migratory cranial neural crest, in the retina, and in the neural tube. Overproduction of XδEF1 in RNA‐injected embryos, like that of XSIP1, reduced the expression of BMP‐dependent genes but only XSIP1 has the ability to induce neural markers. We find that XδEF1 and XSIP1 can both form complexes, although with different efficiency, with Smad3, with the coactivators p300 and pCAF, and with the corepressor CtBP1. Together, these results indicate that δEF1 and SIP1 do not function as antagonists during Xenopus early embryogenesis but do display different repression efficiencies and interaction properties. Developmental Dynamics 235:1491–1500, 2006. © 2006 Wiley‐Liss, Inc.

[1]  L. Garavelli,et al.  Mowat-Wilson syndrome , 2007, Orphanet journal of rare diseases.

[2]  P. Lemaire,et al.  Neural induction in Xenopus requires early FGF signalling in addition to BMP inhibition , 2005, Development.

[3]  C. Stern,et al.  Neural induction requires BMP inhibition only as a late step, and involves signals other than FGF and Wnt antagonists , 2004, Development.

[4]  K. Nitta,et al.  XSIP1 is essential for early neural gene expression and neural differentiation by suppression of BMP signaling. , 2004, Developmental biology.

[5]  E. D. De Robertis,et al.  Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. , 2003, Genes & development.

[6]  D. Darling,et al.  Combination of a Zinc Finger and Homeodomain Required for Protein-Interaction , 2003, Molecular Biology Reports.

[7]  Vincent Bertrand,et al.  Neural Tissue in Ascidian Embryos Is Induced by FGF9/16/20, Acting via a Combination of Maternal GATA and Ets Transcription Factors , 2003, Cell.

[8]  L. Nelles,et al.  Interaction between Smad-interacting Protein-1 and the Corepressor C-terminal Binding Protein Is Dispensable for Transcriptional Repression of E-cadherin* , 2003, Journal of Biological Chemistry.

[9]  J. Massagué,et al.  Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus , 2003, Cell.

[10]  A. Postigo,et al.  Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins , 2003, The EMBO journal.

[11]  A. Postigo.  Opposing functions of ZEB proteins in the regulation of the TGFβ/BMP signaling pathway , 2003, The EMBO journal.

[12]  Yang Shi,et al.  Coordinated histone modifications mediated by a CtBP co-repressor complex , 2003, Nature.

[13]  L. Nelles,et al.  Mice lacking ZFHX1B, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome. , 2003, American journal of human genetics.

[14]  Paul Richardson,et al.  Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[15]  D. Huylebroeck,et al.  Dynamic regulation of Brachyury expression in the amphibian embryo by XSIP1 , 2002, Mechanisms of Development.

[16]  C. Hill.  TGF-β signalling pathways in early Xenopus development , 2001 .

[17]  G. Berx,et al.  The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. , 2001, Molecular cell.

[18]  S. Iuchi,et al.  Three classes of C2H2 zinc finger proteins , 2001, Cellular and Molecular Life Sciences CMLS.

[19]  N. Nomura,et al.  Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease , 2001, Nature Genetics.

[20]  D. Huylebroeck,et al.  SIP1 (Smad interacting protein 1) and deltaEF1 (delta-crystallin enhancer binding factor) are structurally similar transcriptional repressors. , 2001, The Journal of bone and joint surgery. American volume.

[21]  Q. Zhang,et al.  Acetylation of adenovirus E1A regulates binding of the transcriptional corepressor CtBP. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[22]  S. Frisch,et al.  Evidence for a function of CtBP in epithelial gene regulation and anoikis , 2000, Oncogene.

[23]  J. Smith,et al.  Region-specific activation of the Xenopus brachyury promoter involves active repression in ectoderm and endoderm: a study using transgenic frog embryos. , 2000, Development.

[24]  E. Bellefroid,et al.  XSIP1, a Xenopus zinc finger/homeodomain encoding gene highly expressed during early neural development , 2000, Mechanisms of Development.

[25]  A. Fukui,et al.  XSIP1, a member of two-handed zinc finger proteins, induced anterior neural markers in Xenopus laevis animal cap. , 2000, Biochemical and biophysical research communications.

[26]  K. Mizuseki,et al.  Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm. , 2000, Development.

[27]  H. Okamoto,et al.  FGF signaling and the anterior neural induction in Xenopus. , 1999, Developmental biology.

[28]  H. Kondoh,et al.  Identification of CtBP1 and CtBP2 as Corepressors of Zinc Finger-Homeodomain Factor δEF1 , 1999, Molecular and Cellular Biology.

[29]  D. Huylebroeck,et al.  New mode of DNA binding of multi‐zinc finger transcription factors: δEF1 family members bind with two hands to two target sites , 1999, The EMBO journal.

[30]  L. Nelles,et al.  SIP1, a Novel Zinc Finger/Homeodomain Repressor, Interacts with Smad Proteins and Binds to 5′-CACCT Sequences in Candidate Target Genes* , 1999, The Journal of Biological Chemistry.

[31]  D. Dean,et al.  ZEB represses transcription through interaction with the corepressor CtBP. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Hubbard,et al.  Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain , 1998, The EMBO journal.

[33]  J. Massagué,et al.  Physical and Functional Interaction of SMADs and p300/CBP* , 1998, The Journal of Biological Chemistry.

[34]  H. Kondoh,et al.  Two mechanisms in the action of repressor δEF1: binding site competition with an activator and active repression , 1997, Genes to cells : devoted to molecular & cellular mechanisms.

[35]  R. Penzel,et al.  Characterization and early embryonic expression of a neural specific transcription factor xSOX3 in Xenopus laevis. , 1997, The International journal of developmental biology.

[36]  N. Ueno,et al.  Xenopus msx1 mediates epidermal induction and neural inhibition by BMP4. , 1997, Development.

[37]  P. Savatier,et al.  Effect of nerve growth factor on the expression of cell cycle regulatory proteins in PC12 cells: dissection of the neurotrophic response from the anti-mitogenic response. , 1996, Oncogene.

[38]  J. Gurdon,et al.  Normal table of Xenopus laevis (Daudin) , 1995 .

[39]  J. Smith,et al.  Negative control of Xenopus GATA-2 by activin and noggin with eventual expression in precursors of the ventral blood islands. , 1994, Development.

[40]  J B Lawrence,et al.  Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. , 1994, Genes & development.

[41]  H. Kondoh,et al.  Delta-crystallin enhancer binding protein delta EF1 is a zinc finger-homeodomain protein implicated in postgastrulation embryogenesis. , 1993, Development.

[42]  Jonathan M.W. Slack,et al.  The early development of Xenopus laevis: by P. Hausen and M. Riebesell, Springer-Verlag, 1991. £78.50 (vii + 142 pages) ISBN 3 540 53740 6 , 1993 .

[43]  J. Smith,et al.  Expression of a xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction , 1991, Cell.

[44]  P. Krieg,et al.  Primary structure and developmental expression of a large cytoplasmic domain form of Xenopus laevis neural cell adhesion molecule (NCAM). , 1989, Nucleic acids research.

[45]  I. Dawid,et al.  Epidermal keratin gene expressed in embryos of Xenopus laevis. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[46]  J. Faber,et al.  Normal Table of Xenopus Laevis (Daudin) , 1958 .

[47]  G. Chinnadurai.  CtBP family proteins: more than transcriptional corepressors. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[48]  J. Massagué,et al.  Mechanisms of TGF-beta signaling from cell membrane to the nucleus. , 2003, Cell.

[49]  C. Hill.  TGF-beta signalling pathways in early Xenopus development. , 2001, Current opinion in genetics & development.

[50]  R. Harland,et al.  Early development of Xenopus laevis : a laboratory manual , 2000 .

[51]  H. Kondoh,et al.  DeltaEF1, a zinc finger and homeodomain transcription factor, is required for skeleton patterning in multiple lineages. , 1998, Development.

[52]  N. Ueno,et al.  Xenopus msx 1 mediates epidermal induction and neural inhibition by BMP 4 , 1997 .

[53]  T. Kadesch,et al.  Cloning of a cDNA encoding a mouse transcriptional repressor displaying striking sequence conservation across vertebrates. , 1996, Gene.