Tombola, a tesmin/TSO1-family protein, regulates transcriptional activation in the Drosophila male germline and physically interacts with Always early

During male gametogenesis, a developmentally regulated and cell type-specific transcriptional programme is activated in primary spermatocytes to prepare for differentiation of sperm. The Drosophila aly-class meiotic-arrest loci (aly, comr, achi/vis and topi) are essential for activation of transcription of many differentiation-specific genes, and several genes important for meiotic cell cycle progression, thus linking meiotic divisions to cellular differentiation during spermatogenesis. Protein interaction studies suggest that the aly-class gene products form a chromatin-associated complex in primary spermatocytes. We identify, clone and characterise a new aly-class meiotic-arrest gene, tombola (tomb), which encodes a testis-specific CXC-domain protein that interacts with Aly. The tomb mutant phenotype is more like that of aly and comr mutants than that of achi/vis or topi mutants in terms of target gene profile and chromosome morphology. tomb encodes a chromatin-associated protein required for localisation of Aly and Comr, but not Topi, to chromatin Reciprocally, aly and comr, but not topi or achi/vis, are required to maintain the normal localisation of Tomb. tomb and aly might be components of a complex paralogous to the Drosophila dREAM/Myb-MuvB and C. elegans DRM transcriptional regulatory complexes.

[1]  Robert A. H. White,et al.  Drosophila TGIF is essential for developmentally regulated transcription in spermatogenesis , 2003, Development.

[2]  P. O’Farrell,et al.  Mutations of the Drosophila dDP,dE2F, and cyclin E Genes Reveal Distinct Roles for the E2F-DP Transcription Factor and Cyclin E during the G1-S Transition , 1998, Molecular and Cellular Biology.

[3]  N. Dyson,et al.  Retinoblastoma Family 2 is Required In Vivo for the Tissue-Specific Repression of dE2F2 target Genes , 2005, Cell cycle.

[4]  Reuven Agami,et al.  Inhibition of oncogenic transformation by mammalian Lin‐9, a pRB‐associated protein , 2004, The EMBO journal.

[5]  Ting-Yi Lin,et al.  Developmental regulation of transcription by a tissue-specific TAF homolog. , 2001, Genes & development.

[6]  Liam J. McGuffin,et al.  The PSIPRED protein structure prediction server , 2000, Bioinform..

[7]  L. Alphey,et al.  Vectors for the expression of tagged proteins in Drosophila. , 2001, BioTechniques.

[8]  Brian Oliver,et al.  A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults , 2004, Genome Biology.

[9]  R. Mann,et al.  Requirement for two nearly identical TGIF-related homeobox genes in Drosophila spermatogenesis , 2003, Development.

[10]  N. Dyson,et al.  Functional antagonism between E2F family members. , 2001, Genes & development.

[11]  John S. Satterlee,et al.  Native E2F/RBF Complexes Contain Myb-Interacting Proteins and Repress Transcription of Developmentally Controlled E2F Target Genes , 2004, Cell.

[12]  M. Botchan,et al.  Discovery of tMAC: a Drosophila testis-specific meiotic arrest complex paralogous to Myb-Muv B. , 2007, Genes & development.

[13]  A. Boutanaev,et al.  Transcriptional regulation by Modulo integrates meiosis and spermatid differentiation in male germ line , 2006, Proceedings of the National Academy of Sciences.

[14]  J. Belote,et al.  Expression of proteasome subunit isoforms during spermatogenesis in Drosophila melanogaster , 2002, Insect molecular biology.

[15]  H. Lipkin.  Where is the ?c? , 1978 .

[16]  Martin T. Suchorolski,et al.  Testis-specific TAF homologs collaborate to control a tissue-specific transcription program , 2004, Development.

[17]  G. Bouffard,et al.  Gene discovery using computational and microarray analysis of transcription in the Drosophila melanogaster testis. , 2000, Genome research.

[18]  Dahua Chen,et al.  A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell , 2003, Development.

[19]  L. Alphey,et al.  Transcriptional and post-transcriptional control mechanisms coordinate the onset of spermatid differentiation with meiosis I in Drosophila. , 1998, Development.

[20]  P. O’Farrell,et al.  The transcription factor E2F is required for S phase during Drosophila embryogenesis. , 1995, Genes & development.

[21]  I. Royzman,et al.  Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program. , 1997, Genes & development.

[22]  Melissa M. Harrison,et al.  Some C. elegans class B synthetic multivulva proteins encode a conserved LIN-35 Rb-containing complex distinct from a NuRD-like complex , 2006, Proceedings of the National Academy of Sciences.

[23]  H. Horvitz,et al.  The C. elegans gene lin-9,which acts in an Rb-related pathway, is required for gonadal sheath cell development and encodes a novel protein. , 2000, Gene.

[24]  M. Botchan,et al.  Role for a Drosophila Myb-containing protein complex in site-specific DNA replication , 2002, Nature.

[25]  The FlyBase database of the Drosophila genome projects and community literature. , 2003, Nucleic acids research.

[26]  J. Lipsick,et al.  Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  H. White-Cooper,et al.  Transcriptional activation in Drosophila spermatogenesis involves the mutually dependent function of aly and a novel meiotic arrest gene cookie monster , 2003, Development.

[28]  H. Horvitz,et al.  A new class of C. elegans synMuv genes implicates a Tip60/NuA4-like HAT complex as a negative regulator of Ras signaling. , 2004, Developmental cell.

[29]  M. Botchan,et al.  Dm-myb mutant lethality in Drosophila is dependent upon mip130: positive and negative regulation of DNA replication. , 2004, Genes & development.

[30]  R. Renkawitz-Pohl,et al.  Replacement by Drosophila melanogaster Protamines and Mst77F of Histones during Chromatin Condensation in Late Spermatids and Role of Sesame in the Removal of These Proteins from the Male Pronucleus , 2005, Molecular and Cellular Biology.

[31]  R. Raff,et al.  Mutation in a structural gene for a beta-tubulin specific to testis in Drosophila melanogaster. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Olivieri,et al.  Autoradiographic study of nucleic acid synthesis during spermatogenesis in Drosophila melanogaster. , 1965, Mutation research.

[33]  Y. Ohinata,et al.  Germ cell-specific nucleocytoplasmic shuttling protein, tesmin, responsive to heavy metal stress in mouse testes. , 2002, Journal of inorganic biochemistry.

[34]  Melissa M. Harrison,et al.  Identification and Classification of Genes That Act Antagonistically to let-60 Ras Signaling in Caenorhabditis elegans Vulval Development , 2006, Genetics.

[35]  P. G. Wilson,et al.  Coordinate developmental control of the meiotic cell cycle and spermatid differentiation in Drosophila males. , 1996, Development.

[36]  M. Fuller,et al.  Transcription of meiotic cell cycle and terminal differentiation genes depends on a conserved chromatin associated protein, whose nuclear localisation is regulated. , 2000, Development.

[37]  J. Lipsick.  synMuv verite--Myb comes into focus. , 2004, Genes & development.

[38]  Y. Ohinata,et al.  Native Tesmin Is a 60-Kilodalton Protein that Undergoes Dynamic Changes in Its Localization During Spermatogenesis in Mice , 2003, Biology of reproduction.

[39]  A. Fraser,et al.  Chromatin regulation and sumoylation in the inhibition of Ras‐induced vulval development in Caenorhabditis elegans , 2005, The EMBO journal.

[40]  Y. Sancak,et al.  Tissue-Specific TAFs Counteract Polycomb to Turn on Terminal Differentiation , 2005, Science.

[41]  Benjamin Bolival,et al.  Regulation of transcription of meiotic cell cycle and terminal differentiation genes by the testis-specific Zn-finger protein matotopetli , 2004, Development.

[42]  M. Botchan,et al.  Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex. , 2004, Genes & development.

[43]  T. Aigaki,et al.  The gene search system. A method for efficient detection and rapid molecular identification of genes in Drosophila melanogaster. , 1999, Genetics.

[44]  R. Duronio,et al.  Drosophila E2f2 promotes the conversion from genomic DNA replication to gene amplification in ovarian follicle cells. , 2001, Development.