Active repression by unliganded retinoid receptors in development

The retinoid receptors have major roles throughout development, even in the absence of ligand. Here, we summarize an emerging theme whereby gene repression, mediated by unliganded retinoid receptors, can dictate cell fate. In addition to activating transcription, retinoid receptors actively repress gene transcription by recruiting cofactors that promote chromatin compaction. Two developmental processes for which gene silencing by the retinoid receptors is essential are head formation in Xenopus and skeletal development in the mouse. Inappropriate repression, by oncogenic retinoic acid (RA)* receptor (RAR) fusion proteins, blocks myeloid differentiation leading to a rare form of leukemia. Our current understanding of the developmental role of retinoid repression and future perspectives in this field are discussed.

[1]  B. Farboud,et al.  Retinoic Acid Receptors β and γ Do Not Repress, But Instead Activate Target Gene Transcription in Both the Absence and Presence of Hormone Ligand , 2003 .

[2]  L. Sachs,et al.  Nuclear Receptor Corepressor Recruitment by Unliganded Thyroid Hormone Receptor in Gene Repression during Xenopus laevis Development , 2002, Molecular and Cellular Biology.

[3]  O. Hermanson,et al.  N-CoR controls differentiation of neural stem cells into astrocytes , 2002, Nature.

[4]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[5]  G. McArthur,et al.  Retinoic acid receptor antagonism in vivo expands the numbers of precursor cells during granulopoiesis , 2002, Leukemia.

[6]  J. Torchia,et al.  Requirement for RAR-mediated gene repression in skeletal progenitor differentiation , 2002, The Journal of cell biology.

[7]  T. Klimkait,et al.  Promoter of FGF8 reveals a unique regulation by unliganded RARalpha. , 2002, Journal of molecular biology.

[8]  D. O’Carroll,et al.  Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression , 2002, The EMBO journal.

[9]  P. Chambon,et al.  Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development , 2002, Nature Genetics.

[10]  P. Chambon,et al.  Differential expression of the retinoic acid-metabolizing enzymes CYP26A1 and CYP26B1 during murine organogenesis , 2002, Mechanisms of Development.

[11]  H. Gronemeyer,et al.  Co-regulator recruitment and the mechanism of retinoic acid receptor synergy , 2002, Nature.

[12]  R. Evans,et al.  Transcriptional regulation in acute promyelocytic leukemia , 2001, Oncogene.

[13]  L. Sachs,et al.  Involvement of histone deacetylase at two distinct steps in gene regulation during intestinal development in Xenopus laevis , 2001, Developmental dynamics : an official publication of the American Association of Anatomists.

[14]  J. Licht,et al.  Translocations of the RARα gene in acute promyelocytic leukemia , 2001, Oncogene.

[15]  K. Umesono,et al.  Active repression of RAR signaling is required for head formation. , 2001, Genes & development.

[16]  M. Shen,et al.  Msx homeobox genes inhibit differentiation through upregulation of cyclin D1. , 2001, Development.

[17]  F. Wondisford,et al.  An unliganded thyroid hormone receptor causes severe neurological dysfunction , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. Zile.  Function of vitamin A in vertebrate embryonic development. , 2001, The Journal of nutrition.

[19]  P. Chambon,et al.  The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures. , 2001, Genes & development.

[20]  Kristen Jepsen,et al.  Combinatorial Roles of the Nuclear Receptor Corepressor in Transcription and Development , 2000, Cell.

[21]  E. D. De Robertis,et al.  A direct screen for secreted proteins in Xenopus embryos identifies distinct activities for the Wnt antagonists Crescent and Frzb-1 , 2000, Mechanisms of Development.

[22]  J. Ahringer.  NuRD and SIN3 histone deacetylase complexes in development. , 2000, Trends in genetics : TIG.

[23]  U. Dräger,et al.  Retinoids in embryonal development. , 2000, Physiological reviews.

[24]  C. Abate-Shen,et al.  Roles for Msx and Dlx homeoproteins in vertebrate development. , 2000, Gene.

[25]  R. Tsien,et al.  Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator-activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Vicki Rosen,et al.  Regulation of Skeletal Progenitor Differentiation by the Bmp and Retinoid Signaling Pathways , 2000, The Journal of cell biology.

[27]  C. Glass,et al.  The coregulator exchange in transcriptional functions of nuclear receptors. , 2000, Genes & development.

[28]  E. Miska,et al.  Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway. , 2000, Genes & development.

[29]  P. Chambon,et al.  A genetic dissection of the retinoid signalling pathway in the mouse , 1999, Proceedings of the Nutrition Society.

[30]  M. Levine,et al.  Transcriptional coregulators in development. , 1999, Science.

[31]  T. Pieler,et al.  Regionalized metabolic activity establishes boundaries of retinoic acid signalling , 1998, The EMBO journal.

[32]  T. Underhill,et al.  Retinoids and their receptors in skeletal development , 1998, Microscopy research and technique.

[33]  M. Zile.  Vitamin A and embryonic development: an overview. , 1998, The Journal of nutrition.

[34]  Y. Sasai,et al.  Ectodermal patterning in vertebrate embryos. , 1997, Developmental biology.

[35]  K. Schughart,et al.  Retinoic Acid Receptor α Function in Vertebrate Limb Skeletogenesis: a Modulator of Chondrogenesis , 1997, The Journal of cell biology.

[36]  R. Evans,et al.  An essential role for retinoid signaling in anteroposterior neural patterning. , 1997, Development.

[37]  K. Umesono,et al.  SMRT isoforms mediate repression and anti-repression of nuclear receptor heterodimers. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[38]  S. Nishikawa,et al.  Overexpression of retinoic acid receptor alpha suppresses myeloid cell differentiation at the promyelocyte stage. , 1995, Oncogene.

[39]  Myles Brown,et al.  Polarity-specific activities of retinoic acid receptors determined by a co-repressor , 1995, Nature.

[40]  Thorsten Heinzel,et al.  Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor , 1995, Nature.

[41]  D. Davidson,et al.  The function and evolution of Msx genes: pointers and paradoxes. , 1995, Trends in genetics : TIG.

[42]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. , 1994, Development.

[43]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. , 1994, Development.

[44]  P. Pfeffer,et al.  Regional specificity of RARγ isoforms in Xenopus development , 1994, Mechanisms of Development.

[45]  Myriam Alcalay,et al.  The acute promyelocytic leukemia-specific PML-RARα fusion protein inhibits differentiation and promotes survival of myeloid precursor cells , 1993, Cell.

[46]  S. Collins,et al.  A dominant negative retinoic acid receptor blocks neutrophil differentiation at the promyelocyte stage. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[47]  C. Dreyer,et al.  The pattern of retinoic acid receptor γ (RARγ) expression in normal development of Xenopus laevis and after manipulation of the main body axis , 1993, Mechanisms of Development.

[48]  P. Chambon,et al.  Multiplicity generates diversity in the retinoic acid signalling pathways. , 1992, Trends in biochemical sciences.

[49]  A. Dejean,et al.  The retinoic acid receptors. , 1991, Nouvelle revue francaise d'hematologie.

[50]  S. Collins,et al.  Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha) , 1990, Molecular and cellular biology.

[51]  G. Wolf,et al.  Multiple functions of vitamin A. , 1984, Physiological reviews.

[52]  R. Reiter,et al.  Stage-related capacity for limb chondrogenesis in cell culture. , 1977, Developmental biology.

[53]  John H. White,et al.  Ligand-dependent nuclear receptor corepressor LCoR functions by histone deacetylase-dependent and -independent mechanisms. , 2003, Molecular cell.

[54]  B. Farboud,et al.  Retinoic acid receptors beta and gamma do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand. , 2003, Molecular endocrinology.

[55]  J. Licht,et al.  Translocations of the RARalpha gene in acute promyelocytic leukemia. , 2001, Oncogene.

[56]  John J. Wyrick,et al.  Genome-wide location and function of DNA binding proteins. , 2000, Science.

[57]  K. Schughart,et al.  Retinoic Acid Receptor (cid:97) Function in Vertebrate Limb Skeletogenesis: a Modulator of Chondrogenesis , 1997 .

[58]  B. Rodgers,et al.  Downregulation of Msx-2 expression results in chondrogenesis in the medial region of the avian mandible. , 1996, Connective tissue research.

[59]  E. Linney,et al.  Retinoids and mouse embryonic development. , 1995, Vitamins and hormones.

[60]  Hendrik G. Stunnenberg,et al.  Retinoic Acid Receptors , 1995 .

[61]  E. Vitale,et al.  Characterization of the human MSX-1 promoter and an enhancer responsible for retinoic acid induction. , 1994, Cellular & molecular biology research.

[62]  P. Pfeffer,et al.  Regional specificity of RAR gamma isoforms in Xenopus development. , 1994, Mechanisms of development.

[63]  A. Dejean,et al.  The PML-RAR alpha gene product of the t(15;17) translocation inhibits retinoic acid-induced granulocytic differentiation and mediated transactivation in human myeloid cells. , 1994, Oncogene.

[64]  C. Dreyer,et al.  The pattern of retinoic acid receptor gamma (RAR gamma) expression in normal development of Xenopus laevis and after manipulation of the main body axis. , 1993, Mechanisms of development.

[65]  C. Dreyer,et al.  A retinoic acid receptor expressed in the early development of Xenopus laevis. , 1991, Genes & development.