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Leishmania infantum possesses a complex family of histone H2A genes: structural characterization and analysis of expression

Published online by Cambridge University Press:  09 October 2003

M. SOTO ,
L. QUIJADA ,
R. LARRETA ,
S. IBORRA ,
C. ALONSO  and
J. M. REQUENA
M. SOTO
Affiliation:
Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, Madrid, E-28049 Madrid, Spain
L. QUIJADA
Affiliation:
Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, Madrid, E-28049 Madrid, Spain
R. LARRETA
Affiliation:
Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, Madrid, E-28049 Madrid, Spain
S. IBORRA
Affiliation:
Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, Madrid, E-28049 Madrid, Spain
C. ALONSO
Affiliation:
Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, Madrid, E-28049 Madrid, Spain
J. M. REQUENA
Affiliation:
Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, Madrid, E-28049 Madrid, Spain
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Abstract

We have studied the genomic organization and transcription of the histone H2A genes in the protozoan parasite Leishmania infantum. In the parasite genome 2 gene clusters exist, each containing 3 H2A gene copies. Sequence analysesNucleotide sequence data reported in this paper are available in the GenBank™, EMBL and DDBJ databases under the accession numbers AJ419625, AJ419626 and AJ419627. showed the existence of significant sequence divergence among the H2A genes, mainly in their 5′- and 3′-untranslated regions (UTRs). Also, the existence of allelic alternatives has been evidenced. Based on the divergence in the 3′UTR regions, we have defined 3 classes of H2A transcripts, which are present at different levels in L. infantum promastigotes. However, transcription of the 3 classes of H2A genes occurs at similar levels, as measured by nuclear run-on assays, indicating that their abundance is regulated post-transcriptionally. Also, differences in regulation were observed among the H2A transcripts: the levels of transcripts with 3′-UTR type I and type III are affected by growth phase whereas transcripts with 3′-UTR type II, that are barely detected, remain constant. It is likely that the complexity, in both gene organization and differential expression exhibited by the L. infantum H2A genes, is imposed by the nature of the post-transcriptional mechanisms of regulation operating in this parasite.

Keywords

Leishmania infantummulti-gene familydifferential gene expressionpost-transcriptional regulationallelic polymorphism
Type
Research Article
Information
Parasitology , Volume 127 , Issue 2 , August 2003 , pp. 95 - 105
Copyright
2003 Cambridge University Press

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References

REFERENCES

BHATIA, A., SANYAL, R., PARAMCHUK, W. & GEDAMU, L. (1998). Isolation, characterization and disruption of the casein kinase II alpha subunit gene of Leishmania chagasi. Molecular and Biochemical Parasitology 92, 195–206.CrossRefGoogle Scholar
BONTEMPI, E. J., PORCEL, B. M., HENRIKSSON, J., CARLSSON, L., RYDAKER, M., SEGURA, E. L., RUIZ, A. M. & PETERSSON, U. (1994). Genes for histone H3 in Trypanosoma cruzi. Molecular and Biochemical Parasitology 66, 147–151.CrossRefGoogle Scholar
BOUCHER, N., WU, Y., DUMAS, C., DUBE, M., SERENO, D., BRETON, M. & PAPADOPOULOU, B. (2002). A common mechanism of stage-regulated gene expression in Leishmania mediated by a conserved 3′-untranslated region element. Journal of Biological Chemistry 277, 19511–19520.CrossRefGoogle Scholar
BURCHMORE, R. J. S. & LANDFEAR, S. M. (1998). Differential regulation of multiple glucose transporter genes in Leishmania mexicana. Journal of Biological Chemistry 273, 29118–29126.CrossRefGoogle Scholar
CHAREST, H., ZHANG, W. W. & MATLASHEWSKI, G. (1996). The developmental expression of Leishmania donovani A2 amastigote-specific genes is post-transcriptionally mediated and involves elements located in the 3′-untranslated region. Journal of Biological Chemistry 271, 17081–17090.CrossRefGoogle Scholar
CHOMCZYNSK, P. & SACCHI, M. (1987). Single-step method of RNA extraction by acid guanidinium thiocyanathe-phenol-chloroform extraction. Analytical Biochemistry 162, 156–159.Google Scholar
CLAYTON, C., ADAMS, M., ALMEIDA, R., BALTZ, T., BARRET, M., BASTIEN, P., BELLI, S., BEVERLEY, S., BITEAU, N., BLACKWELL, J., BLAINEAU, C., BOSHART, M., BRINGAUD, F., CROSS, G., CRUZ, A., DEGRAVE, W., DONELSON, J., EL-SAYED, N., FU, G., ERSFELD, K., GIBSON, W., GULL, K., IVENS, A., KELLY, J., LAWSON, D., LEBOWITZ, J., MAJIWA, P., MATTHEWS, K., MELVILLE, S., MERLIN, G., MICHELS, P., MYLER, P., NORRISH, A., OPPERDOES, F., PAPADOPOULOU, B., PARSONS, M., SEEBECK, T., SMITH, D., STUART, K., TURNER, M., ULLU, E. & VANHAMME, L. (1998). Genetic nomenclature for Trypanosoma and Leishmania. Molecular and Biochemical Parasitology 97, 221–224.CrossRefGoogle Scholar
COULSON, R. M., CONNOR, V., CHEN, J. C. & AJIOKA, J. W. (1996). Differential expression of Leishmania major beta-tubulin genes during the acquisition of promastigote infectivity. Molecular and Biochemical Parasitology 82, 227–236.CrossRefGoogle Scholar
DONELSON, J. E., GARDNER, M. J. & EL-SAYED, N. M. (1999). More surprises from Kinetoplastida. Proceedings of the National Academy of Sciences, USA 96, 2579–2581.CrossRefGoogle Scholar
ERSFELD, K., DOCHERTY, R., ALSFORD, S. & GULL, K. (1996). A fluorescence in situ hybridisation study of the regulation of histone mRNA level during the cell cycle of Trypanosoma brucei. Molecular and Biochemical Parasitology 81, 201–209.CrossRefGoogle Scholar
GALANTI, N., GALINDO, M., SABAJ, V., ESPINOZA, I. & TORO, G. C. (1998). Histone genes in Trypanosomatids. Parasitology Today 14, 64–70.CrossRefGoogle Scholar
GARCÍA-SALCEDO, J. A., GIJÓN, P. & PAYS, E. (1999). Regulated transcription of the histone H2B of Trypanosoma brucei. European Journal of Biochemistry 264, 717–723.CrossRefGoogle Scholar
GARCÍA-SALCEDO, J. A., OLIVER, J., STOCK, R. P. & GONZALEZ, A. (1994). Molecular characterization and transcription of the histone H2B gene from the protozoan parasite Trypanosoma cruzi. Molecular Microbiology 13, 1033–1043.CrossRefGoogle Scholar
GENSKE, J. E., CAIRNS, B. R., STACK, S. P. & LANDFEAR, S. M. (1991). Structure and regulation of histone H2B mRNAs from Leishmania enriettii. Molecular and Cellular Biology 11, 240–249.CrossRefGoogle Scholar
GÖPFERT, U., GOEHRING, N., KLEIN, C. & ILG, T. (1999). Proteophosphoglycans of Leishmania mexicana: molecular cloning and characterization of the Leishmania mexicana ppg2 gene encoding the proteophosphoglycans aPPG that are secreted by amastigotes and promastigotes. The Biochemical Journal 344, 787–795.CrossRefGoogle Scholar
IVENS, A. C., LEWIS, S. M., BAGHERZADEH, A., ZHANG, L., CHAN, H. M. & SMITH, D. F. (1998). A physical map of the Leishmania major Friedlin genome. Genome Research 8, 135–145.CrossRefGoogle Scholar
LANDFEAR, S. M. (2001). Molecular genetics of nucleoside transporters in Leishmania and African trypanosomes. Biochemical Pharmacology 62, 149–155.CrossRefGoogle Scholar
LERACH, H., DIAMOND, D., WOZNEY, J. M. & BOEDTKER, H. (1977). RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry 16, 4743–4751.CrossRefGoogle Scholar
LUKES, J. & MASLOV, D. A. (2000). Unexpectedly high variability of the histone H4 gene in Leishmania. Parasitology Research 86, 259–261.Google Scholar
MACHADO, C. A. & AYALA, F. J. (2001). Nucleotide sequences provide evidence of genetic exchange among distantly related lineages of Trypanosoma cruzi. Proceedings of the National Academy of Sciences, USA 98, 7396–7401.CrossRefGoogle Scholar
MARAÑÓN, C., PUERTA, C., ALONSO, C. & LÓPEZ, M. C. (1998). Control mechanisms of the H2A genes expression in Trypanosoma cruzi. Molecular and Biochemical Parasitology 92, 313–324.CrossRefGoogle Scholar
MARAÑÓN, C., THOMAS, M. C., PUERTA, C., ALONSO, C. & LÓPEZ, M. C. (2000). The stability and maturation of the H2A histone mRNAs from Trypanosoma cruzi are implicated in their post-transcriptional regulation. Biochimica et Biophysica Acta 1490, 1–10.CrossRefGoogle Scholar
OSLEY, M. A. (1991). The regulation of histones synthesis in the cell cycle. Annual Review of Biochemistry 60, 827–861.CrossRefGoogle Scholar
PUERTA, C., MARTÍN, J., ALONSO, C. & LÓPEZ, M. C. (1994). Isolation and characterization of the gene encoding histone H2A from Trypanosoma cruzi. Molecular and Biochemical Parasitology 64, 1–10.CrossRefGoogle Scholar
QUIJADA, L., MOREIRA, D., SOTO, M., ALONSO, C. & REQUENA, J. M. (1997 a). Efficient 5′-End labelling of oligonucleotides containing self-complementary sequences. Biotechniques 23, 658–660.Google Scholar
QUIJADA, L., SOTO, M., ALONSO, C. & REQUENA, J. M. (1997 b). Analysis of post-transcriptional regulation operating on transcription products of the tandemly linked Leishmania infantum hsp70 genes. Journal of Biological Chemistry 272, 4493–4499.Google Scholar
QUIJADA, L., SOTO, M., ALONSO, C. & REQUENA, J. M. (2000). Identification of a putative regulatory element in the 3′-untranslated region that controls expression of HSP70 in Leishmania infantum. Molecular and Biochemical Parasitology 110, 79–91.CrossRefGoogle Scholar
RAMAMOORTHY, R., DONELSON, J. E., PAETZ, K. E., MAYBODI, M., ROBERTS, S. C. & WILSON, M. E. (1992). Three distinct RNAs for the surface protease gp63 are differentially expressed during development of Leishmania donovani chagasi promastigotes to an infectious form. Journal of Biological Chemistry 267, 1888–1895.Google Scholar
RAMAMOORTHY, R., SWIHART, K. G., McCOY, J. J., WILSON, M. E. & DONELSON, J. E. (1995). Intergenic regions between tandem gp63 genes influence the differential expression of gp63 RNAs in Leishmania chagasi promastigotes. Journal of Biological Chemistry 270, 12133–12139.CrossRefGoogle Scholar
RAVEL, C., DUBESSAY, P., BLACKWELL, J. M., IVENS, A. C., BASTIEN, P. & THE LEISHMANIA GENOME NETWORK (1998). The complete chromosomal organization of the reference strain of the Leishmania genome project, L. major ‘Friedlin’. Parasitology Today 14, 301–303.CrossRefGoogle Scholar
RECINOS, R. F., KIRCHHOFF, L. V. & DONELSON, J. E. (2001). Cell cycle expression of histone genes in Trypanosoma cruzi . Molecular and Biochemical Parasitology 113, 215–222.CrossRefGoogle Scholar
REQUENA, J. M., LÓPEZ, M. C., JIMENEZ-RUIZ, A., DE LA TORRE, J. C. & ALONSO, C. (1988). A head to tail organization of hsp70 genes in Trypanosoma cruzi . Nucleic Acids Research 16, 387–395.Google Scholar
REVELARD, P., LIPS, S. & PAYS, E. (1993). Alternative splicing within and between alleles of the ATPase gene 1 locus of Trypanosoma brucei. Molecular and Biochemical Parasitology 62, 93–102.CrossRefGoogle Scholar
SAMBROOK, L., FRITSCH, E. F. & MANIATIS, T. (1989). Molecular Cloning: a Laboratory Manual, 2nd Edn. Cold Spring Harbor Laboratory, Cold Spring Harbor NY.
SOARES, C. M. A., DE CARVALHO, E. F., URMENYI, T. P., CARVALHO, J. F. O., DE CASTRO, F. T. & RONDINELLI, E. (1989). α- and β-tubulin mRNAs of Trypanosoma cruzi originated from a single multicistronic transcript. FEBS Letters 250, 497–502.CrossRefGoogle Scholar
SOGIN, M. L., ELWOOD, H. J. & GUNDERSON, J. H. (1986). Evolutionary diversity of eukaryotic small-subunit rRNA genes. Proceedings of the National Academy of Sciences, USA 83, 1383–1387.CrossRefGoogle Scholar
SOTO, M., QUIJADA, L., ALONSO, C. & REQUENA, J. M. (2000). Histone synthesis in Leishmania infantum is tightly linked to DNA replication by a translational control. The Biochemical Journal 346, 99–105.CrossRefGoogle Scholar
SOTO, M., REQUENA, J. M., GARCÍA, M., GÓMEZ, L. C., NAVARRETE, I. & ALONSO, C. (1993). Genomic organization and expression of two independent gene arrays coding for two antigenic acidic ribosomal proteins of Leishmania. Journal of Biological Chemistry 268, 21835–21843.Google Scholar
SOTO, M., REQUENA, J. M., GÓMEZ, L. C., NAVARRETE, I. & ALONSO, C. (1992). Molecular characterization of a Leishmania donovani infantum antigen identified as histone H2A. European Journal of Biochemistry 205, 211–216.CrossRefGoogle Scholar
SOTO, M., REQUENA, J. M., MORALES, G. & ALONSO, C. (1994). The Leishmania infantum histone H3 posseses an extremely divergent N-terminal domain. Biochimica et Biophysica Acta 1219, 533–535.CrossRefGoogle Scholar
SOTO, M., REQUENA, J. M., MOREIRA, D. & ALONSO, C. (1995). Assignment of genes to Leishmania infantum chromosomes: karyotipe and ploidy. FEMS Microbiology Letters 129, 27–32.Google Scholar
SOTO, M., REQUENA, J. M., QUIJADA, L. & ALONSO, C. (1996). Organization, transcription and regulation of the Leishmania infantum histone H3 genes. Biochemical Journal 318, 813–819.CrossRefGoogle Scholar
SOTO, M., REQUENA, J. M., QUIJADA, L. & ALONSO, C. (1997). Molecular cloning and analysis of expression of the Leishmania infantum histone H4 genes. Molecular and Biochemical Parasitology 90, 439–447.CrossRefGoogle Scholar
SOTO, M., REQUENA, J. M., QUIJADA, L. & ALONSO, C. (1998). Multicomponent chimeric antigen for serodiagnosis of canine visceral leishmaniasis. Journal of Clinical Microbiology 36, 58–63.Google Scholar
STEIN, G. S., STEIN, J. L., VAN WIJNEN, A. J. & LIAN, J. B. (1994). Histone gene transcription: a model for responsiveness to an integrated series of regulatory signals mediating cell cycle control and proliferation/differentiation interrelationships. Journal of Cellular Biochemistry 54, 393–404.CrossRefGoogle Scholar
STILES, J. K., HICOCK, P. I., SHAH, P. H. & MEADE, J. C. (1999). Genomic organization, transcription, splicing and gene regulation in Leishmania. Annals of Tropical Medicine and Parasitology 93, 781–807.CrossRefGoogle Scholar
THATCHER, T. H. & GOROVSKY, M. A. (1994). Phylogenetic analysis of the core histones H2A, H2B, H3 and H4. Nucleic Acids Research 22, 174–179.CrossRefGoogle Scholar
USACHENKO, S. I., BAVYKIN, S. G., GAVIN, I. M. & BRADBURY, E. M. (1994). Rearrangement of the histone H2A C-terminal domain in the nucleosome. Proceedings of the National Academy of Sciences, USA 91, 6845–6849.CrossRefGoogle Scholar
WINCKER, P., RAVEL, C., BLAINEAU, C., PAGES, M., JAUFFRET, Y., DEDET, J.-P. & BASTIEN, P. (1996). The Leishmania genome comprises 36 chromosomes conserved across widely divergent human pathogenic species. Nucleic Acids Research 24, 1688–1694.CrossRefGoogle Scholar