Control of human testis-specific gene expression


Autoři: Jay C. Brown aff001
Působiště autorů: Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America aff001
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0215184

Souhrn

Background

As a result of decades of effort by many investigators we now have an advanced level of understanding about several molecular systems involved in the control of gene expression. Examples include CpG islands, promoters, mRNA splicing and epigenetic signals. It is less clear, however, how such systems work together to integrate the functions of a living organism. Here I describe the results of a study to test the idea that a contribution might be made by focusing on genes specifically expressed in a particular tissue, the human testis.

Experimental design

A database of 239 testis-specific genes was accumulated and each was examined for the presence of features relevant to control of gene expression. These include: (1) the presence of a promoter, (2) the presence of a CpG island (CGI) within the promoter, (3) the presence in the promoter of a transcription factor binding site near the transcription start site, (4) the level of gene expression, and (5) the above features in genes of testis-specific cell types such as spermatocyte and spermatid that differ in their extent of differentiation.

Results

Of the 107 database genes with an annotated promoter, 56 were found to have one or more transcription factor binding sites near the transcription start site. Three of the binding sites observed, Pax-5, AP-2αA and GRα, stand out in abundance suggesting they may be involved in testis-specific gene expression. Compared to less differentiated testis-specific cells, genes of more differentiated cells were found to be (1) more likely to lack a CGI, (2) more likely to lack introns and (3) higher in expression level. The results suggest genes of more differentiated cells have a reduced need for CGI-based regulatory repression, reduced usage of gene splicing and a smaller set of expressed proteins.

Klíčová slova:

Biology and life sciences – Genetics – Gene expression – DNA transcription – Gene regulation – Genomics – Genome analysis – Genomic databases – Biochemistry – Proteins – DNA-binding proteins – Transcription factors – Regulatory proteins – Developmental biology – Cell differentiation – Computational biology – Cell biology – Cellular types – Animal cells – Germ cells – Sperm – Research and analysis methods – Database and informatics methods – Biological databases – Bioinformatics – Sequence analysis – Sequence databases


Zdroje

1. Gagniuc P, Ionescu-Tirgoviste C. Eukaryotic genomes may exhibit up to 10 generic classes of gene promoters. BMC Genomics. 2012;13:512. doi: 10.1186/1471-2164-13-512 23020586

2. Deaton AM, Bird A. CpG islands and the regulation of transcription. Genes Dev. 2011;25(10):1010–22. doi: 10.1101/gad.2037511 21576262

3. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057–68. doi: 10.1038/nbt.1685 20944598

4. Lee TI, Young RA. Transcription of eukaryotic protein-coding genes. Annu Rev Genet. 2000;34:77–137. doi: 10.1146/annurev.genet.34.1.77 11092823

5. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, et al. Super-enhancers in the control of cell identity and disease. Cell. 2013;155(4):934–47. doi: 10.1016/j.cell.2013.09.053 24119843

6. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012;485(7398):376–80. doi: 10.1038/nature11082 22495300

7. Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003;72:291–336. doi: 10.1146/annurev.biochem.72.121801.161720 12626338

8. Djureinovic D, Fagerberg L, Hallstrom B, Danielsson A, Lindskog C, Uhlen M, et al. The human testis-specific proteome defined by transcriptomics and antibody-based profiling. Mol Hum Reprod. 2014;20(6):476–88. doi: 10.1093/molehr/gau018 24598113

9. Trainer TD. Histology of the normal testis. Am J Surg Pathol. 1987;11(10):797–809. doi: 10.1097/00000478-198710000-00007 3661824

10. Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science 2015;347(6220):1260419. doi: 10.1126/science.1260419 25613900

11. Liu F, Jin S, Li N, Liu X, Wang H, Li J. Comparative and functional analysis of testis-specific genes. Boil Pharm. Bull. 2011/34(1):28–35.

12. Davuluri RV, Grosse I, Zhang MQ. Computational identification of promoters and first exons in the human genome. Nat Genet. 2001;29(4):412–7. doi: 10.1038/ng780 11726928

13. Brown JC. Control of human gene expression: High abundance of divergent transcription in genes containing both INR and BRE elements in the core promoter. PLoS One. 2018;13(8):e0202927. doi: 10.1371/journal.pone.0202927 30138429

14. Vinson C, Chatterjee R. CG methylation. Epigenomics. 2012;4(6):655–63. doi: 10.2217/epi.12.55 23244310

15. Zhu J, He F, Hu S, Yu J. On the nature of human housekeeping genes. Trends Genet. 2008;24(10):481–4. doi: 10.1016/j.tig.2008.08.004 18786740

16. Bogdanovic O, Veenstra GJ. DNA methylation and methyl-CpG binding proteins: developmental requirements and function. Chromosoma. 2009;118(5):549–65. doi: 10.1007/s00412-009-0221-9 19506892

17. Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011;25(18):1915–27. doi: 10.1101/gad.17446611 21890647

18. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89. doi: 10.1101/gr.132159.111 22955988

19. Grzybowska EA. Human intronless genes: functional groups, associated diseases, evolution, and mRNA processing in absence of splicing. Biochem Biophys Res Commun. 2012;424(1):1–6. doi: 10.1016/j.bbrc.2012.06.092 22732409

20. Lei H, Dias AP, Reed R. Export and stability of naturally intronless mRNAs require specific coding region sequences and the TREX mRNA export complex. Proc Natl Acad Sci U S A. 2011;108(44):17985–90. doi: 10.1073/pnas.1113076108 22010220

21. Smale ST, Kadonaga JT. The RNA polymerase II core promoter. Annu Rev Biochem. 2003;72:449–79. doi: 10.1146/annurev.biochem.72.121801.161520 12651739

22. Roy AL, Singer DS. Core promoters in transcription: old problem, new insights. Trends Biochem Sci. 2015;40(3):165–71. doi: 10.1016/j.tibs.2015.01.007 25680757

23. Ross MH, Pawlina W. Histology: a text and atlas: with correlated cell and molecular biology. 5th ed. Baltimore MD: Lippincott Wiliams & Wilkins; 2006. xvii, 906 p. p.

24. Hill, M.A. (2019, March 18) Embryology Spermatozoa Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Spermatozoa_Development.

25. Li G, Ruan X, Auerbach RK, Sandhu KS, Zheng M, Wang P, et al. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell. 2012;148(1–2):84–98. doi: 10.1016/j.cell.2011.12.014 22265404

26. Tang Z, Luo OJ, Li X, Zheng M, Zhu JJ, Szalaj P, et al. CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. Cell. 2015; 163(7):1611–27. doi: 10.1016/j.cell.2015.11.024 26686651

27. van Steensel B, Belmont AS. Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression. Cell. 2017;169(5):780–91. doi: 10.1016/j.cell.2017.04.022 28525751

28. Weintraub AS, Li CH, Zamudio AV, Sigova AA, Hannett NM, Day DS, et al. YY1 Is a Structural Regulator of Enhancer-Promoter Loops. Cell. 2017;171(7):1573–88 e28. doi: 10.1016/j.cell.2017.11.008 29224777

29. Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013; 154(1):26–46. doi: 10.1016/j.cell.2013.06.020 23827673

30. Nott A, Meislin SH, Moore MJ. A quantitative analysis of intron effects on mammalian gene expression. RNA. 2003;9(5):607–17. doi: 10.1261/rna.5250403 12702819

31. Shaul O. How introns enhance gene expression. Int J Biochem Cell Biol. 2017;91(Pt B):145–55. doi: 10.1016/j.biocel.2017.06.016 28673892

32. Adams B, Dorfler P, Aguzzi A, Kozmik Z, Urbanek P, Maurer-Fogy I, et al. Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. Genes Dev. 1992;6(9):1589–607. doi: 10.1101/gad.6.9.1589 1516825

33. McManus S, Ebert A, Salvagiotto G, Medvedovic J, Sun Q, Tamir I, et al. The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells. EMBO J. 2011;30(12):2388–404. doi: 10.1038/emboj.2011.140 21552207

34. Gestri G, Osborne RJ, Wyatt AW, Gerrelli D, Gribble S, Stewart H, et al. Reduced TFAP2A function causes variable optic fissure closure and retinal defects and sensitizes eye development to mutations in other morphogenetic regulators. Hum Genet. 2009; 126(6):791–803. doi: 10.1007/s00439-009-0730-x 19685247

35. Schorle H, Meier P, Buchert M, Jaenisch R, Mitchell PJ. Transcription factor AP-2 essential for cranial closure and craniofacial development. Nature. 1996;381(6579):235–8. doi: 10.1038/381235a0 8622765

36. Pauls K, Jager R, Weber S, Wardelmann E, Koch A, Buttner R, et al. Transcription factor AP-2gamma, a novel marker of gonocytes and seminomatous germ cell tumors. Int J Cancer. 2005;115(3):470–7. doi: 10.1002/ijc.20913 15700319

37. Eckert D, Buhl S, Weber S, Jager R, Schorle H. The AP-2 family of transcription factors. Genome Biol. 2005;6(13):246. doi: 10.1186/gb-2005-6-13-246 16420676

38. Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol. 2013;132(5):1033–44. doi: 10.1016/j.jaci.2013.09.007 24084075

39. Schultz R, Isola J, Parvinen M, Honkaniemi J, Wikstrom AC, Gustafsson JA, et al. Localization of the glucocorticoid receptor in testis and accessory sexual organs of male rat. Mol Cell Endocrinol. 1993;95(1–2):115–20. doi: 10.1016/0303-7207(93)90036-j 8243801

40. Ahn J, Park YJ, Chen P, Lee TJ, Jeon YJ Croce CM, et al. Comparative expression profiling of testis-enriched genes regulated during development of spermatogonial cells. PLoS One. 2017;12(4):e175787.

41. Mikhaylova LM, Nguyen K, Nurminsky DI. Analysis of the Drosophila melanogaster testis transcriptome reveals coordinate regulation of paralogous genes. Genetics 2008;179(1):305–315. doi: 10.1534/genetics.107.080267 18493055


Článek vyšel v časopise

PLOS One


2019 Číslo 9
Nejčtenější tento týden