Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1997 Jun 1;25(11):2197–2204. doi: 10.1093/nar/25.11.2197

Control of mouse U1 snRNA gene expression during in vitro differentiation of mouse embryonic stem cells.

Y Cheng 1, E Lund 1, B W Kahan 1, J E Dahlberg 1
PMCID: PMC146704  PMID: 9153321

Abstract

Early in mouse development, two classes of U1 RNAs, mU1a and mU1b, are synthesized, but as development proceeds, transcription of the embryo-specific mU1b genes is selectively down-regulated to a barely detectable level. We show here that during in vitro differentiation of mouse embryonic stem (ES) cells, both exogenously introduced and endogenous U1b genes are subject to normal developmental regulation. Thus, ES cells represent a convenient isogenic system for studying the control of expression of developmentally regulated snRNA genes. Using this system, we have identified a region in the proximal 5'flanking region, located outside the PSE element, that is responsible for differential transcription of the mU1a and mU1b genes in both developing cells and transiently transfected NIH 3T3 cells.

Full Text

The Full Text of this article is available as a PDF (233.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ares M., Jr, Chung J. S., Giglio L., Weiner A. M. Distinct factors with Sp1 and NF-A specificities bind to adjacent functional elements of the human U2 snRNA gene enhancer. Genes Dev. 1987 Oct;1(8):808–817. doi: 10.1101/gad.1.8.808. [DOI] [PubMed] [Google Scholar]
  2. Ares M., Jr, Mangin M., Weiner A. M. Orientation-dependent transcriptional activator upstream of a human U2 snRNA gene. Mol Cell Biol. 1985 Jul;5(7):1560–1570. doi: 10.1128/mcb.5.7.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bach M., Krol A., Lührmann R. Structure-probing of U1 snRNPs gradually depleted of the U1-specific proteins A, C and 70k. Evidence that A interacts differentially with developmentally regulated mouse U1 snRNA variants. Nucleic Acids Res. 1990 Feb 11;18(3):449–457. doi: 10.1093/nar/18.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bernués J., Simmen K. A., Lewis J. D., Gunderson S. I., Polycarpou-Schwarz M., Moncollin V., Egly J. M., Mattaj I. W. Common and unique transcription factor requirements of human U1 and U6 snRNA genes. EMBO J. 1993 Sep;12(9):3573–3585. doi: 10.1002/j.1460-2075.1993.tb06031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blatt C., Saxe D., Marzluff W. F., Lobo S., Nesbitt M. N., Simon M. I. Mapping and gene order of U1 small nuclear RNA, endogenous viral env sequence, amylase, and alcohol dehydrogenase-3 on mouse chromosome 3. Somat Cell Mol Genet. 1988 Mar;14(2):133–142. doi: 10.1007/BF01534398. [DOI] [PubMed] [Google Scholar]
  6. Ciliberto G., Buckland R., Cortese R., Philipson L. Transcription signals in embryonic Xenopus laevis U1 RNA genes. EMBO J. 1985 Jun;4(6):1537–1543. doi: 10.1002/j.1460-2075.1985.tb03814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cáceres J. F., McKenzie D., Thimmapaya R., Lund E., Dahlberg J. E. Control of mouse U1a and U1b snRNA gene expression by differential transcription. Nucleic Acids Res. 1992 Aug 25;20(16):4247–4254. doi: 10.1093/nar/20.16.4247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doetschman T. C., Eistetter H., Katz M., Schmidt W., Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol. 1985 Jun;87:27–45. [PubMed] [Google Scholar]
  9. Evans M. J., Kaufman M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981 Jul 9;292(5819):154–156. doi: 10.1038/292154a0. [DOI] [PubMed] [Google Scholar]
  10. Forbes D. J., Kirschner M. W., Caput D., Dahlberg J. E., Lund E. Differential expression of multiple U1 small nuclear RNAs in oocytes and embryos of Xenopus laevis. Cell. 1984 Oct;38(3):681–689. doi: 10.1016/0092-8674(84)90263-0. [DOI] [PubMed] [Google Scholar]
  11. Fritz A., Parisot R., Newmeyer D., De Robertis E. M. Small nuclear U-ribonucleoproteins in Xenopus laevis development. Uncoupled accumulation of the protein and RNA components. J Mol Biol. 1984 Sep 15;178(2):273–285. doi: 10.1016/0022-2836(84)90144-x. [DOI] [PubMed] [Google Scholar]
  12. Green M. R. Biochemical mechanisms of constitutive and regulated pre-mRNA splicing. Annu Rev Cell Biol. 1991;7:559–599. doi: 10.1146/annurev.cb.07.110191.003015. [DOI] [PubMed] [Google Scholar]
  13. Grimm C., Stefanovic B., Schümperli D. The low abundance of U7 snRNA is partly determined by its Sm binding site. EMBO J. 1993 Mar;12(3):1229–1238. doi: 10.1002/j.1460-2075.1993.tb05764.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Han Y. M., Dahlberg J., Lund E., Manley J. L., Prives C. SV40 T-antigen-binding sites within the 5'-flanking regions of human U1 and U2 genes. Gene. 1991 Dec 30;109(2):219–231. doi: 10.1016/0378-1119(91)90612-f. [DOI] [PubMed] [Google Scholar]
  15. Hanley B. A., Schuler M. A. Developmental expression of plant snRNAs. Nucleic Acids Res. 1991 Nov 25;19(22):6319–6325. doi: 10.1093/nar/19.22.6319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Henry R. W., Sadowski C. L., Kobayashi R., Hernandez N. A TBP-TAF complex required for transcription of human snRNA genes by RNA polymerase II and III. Nature. 1995 Apr 13;374(6523):653–656. doi: 10.1038/374653a0. [DOI] [PubMed] [Google Scholar]
  17. Hernandez N., Lucito R. Elements required for transcription initiation of the human U2 snRNA gene coincide with elements required for snRNA 3' end formation. EMBO J. 1988 Oct;7(10):3125–3134. doi: 10.1002/j.1460-2075.1988.tb03179.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hooper M., Hardy K., Handyside A., Hunter S., Monk M. HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature. 1987 Mar 19;326(6110):292–295. doi: 10.1038/326292a0. [DOI] [PubMed] [Google Scholar]
  19. Howard E. F., Michael S. K., Dahlberg J. E., Lund E. Functional, developmentally expressed genes for mouse U1a and U1b snRNAs contain both conserved and non-conserved transcription signals. Nucleic Acids Res. 1986 Dec 22;14(24):9811–9825. doi: 10.1093/nar/14.24.9811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kato N., Harada F. New U1 RNA species found in Friend SFFV (spleen focus forming virus)-transformed mouse cells. J Biol Chem. 1985 Jun 25;260(12):7775–7782. [PubMed] [Google Scholar]
  21. Lea I., Moore H. D., Latchman D. S. Differential expression of the mouse U1a and U1b SnRNA genes is not dependent on sequence differences in the octamer motif. Biochem J. 1991 Aug 1;277(Pt 3):719–722. doi: 10.1042/bj2770719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lindenbaum M. H., Grosveld F. An in vitro globin gene switching model based on differentiated embryonic stem cells. Genes Dev. 1990 Dec;4(12A):2075–2085. doi: 10.1101/gad.4.12a.2075. [DOI] [PubMed] [Google Scholar]
  23. Lo P. C., Mount S. M. Drosophila melanogaster genes for U1 snRNA variants and their expression during development. Nucleic Acids Res. 1990 Dec 11;18(23):6971–6979. doi: 10.1093/nar/18.23.6971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lobo S. M., Marzluff W. F., Seufert A. C., Dean W. L., Schultz G. A., Simerly C., Schatten G. Localization and expression of U1 RNA in early mouse embryo development. Dev Biol. 1988 Jun;127(2):349–361. doi: 10.1016/0012-1606(88)90321-1. [DOI] [PubMed] [Google Scholar]
  25. Lund E., Dahlberg J. E. Differential accumulation of U1 and U4 small nuclear RNAs during Xenopus development. Genes Dev. 1987 Mar;1(1):39–46. doi: 10.1101/gad.1.1.39. [DOI] [PubMed] [Google Scholar]
  26. Lund E., Dahlberg J. E. True genes for human U1 small nuclear RNA. Copy number, polymorphism, and methylation. J Biol Chem. 1984 Feb 10;259(3):2013–2021. [PubMed] [Google Scholar]
  27. Lund E., Kahan B., Dahlberg J. E. Differential control of U1 small nuclear RNA expression during mouse development. Science. 1985 Sep 20;229(4719):1271–1274. doi: 10.1126/science.2412294. [DOI] [PubMed] [Google Scholar]
  28. Lund E., Nesbitt M. N. The embryonic and adult mouse U1 snRNA genes map to different chromosomal loci. Somat Cell Mol Genet. 1988 Mar;14(2):143–148. doi: 10.1007/BF01534399. [DOI] [PubMed] [Google Scholar]
  29. Martin G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634–7638. doi: 10.1073/pnas.78.12.7634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mattaj I. W., Lienhard S., Jiricny J., De Robertis E. M. An enhancer-like sequence within the Xenopus U2 gene promoter facilitates the formation of stable transcription complexes. Nature. 1985 Jul 11;316(6024):163–167. doi: 10.1038/316163a0. [DOI] [PubMed] [Google Scholar]
  31. Matthias P. D., Bernard H. U., Scott A., Brady G., Hashimoto-Gotoh T., Schütz G. A bovine papilloma virus vector with a dominant resistance marker replicates extrachromosomally in mouse and E. coli cells. EMBO J. 1983;2(9):1487–1492. doi: 10.1002/j.1460-2075.1983.tb01612.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Michael S. K., Hilgers J., Kozak C., Whitney J. B., 3rd, Howard E. F. Characterization and mapping of DNA sequence homologous to mouse U1a1 snRNA: localization on chromosome 11 near the Dlb-1 and Re loci. Somat Cell Mol Genet. 1986 May;12(3):215–223. doi: 10.1007/BF01570780. [DOI] [PubMed] [Google Scholar]
  33. Mittal V., Hernandez N. Role for the amino-terminal region of human TBP in U6 snRNA transcription. Science. 1997 Feb 21;275(5303):1136–1140. doi: 10.1126/science.275.5303.1136. [DOI] [PubMed] [Google Scholar]
  34. Miyake J. H., Botros I. W., Stumph W. E. Differential protein-DNA interactions at the promoter and enhancer regions of developmentally regulated U4 snRNA genes. Gene Expr. 1992;2(2):161–173. [PMC free article] [PubMed] [Google Scholar]
  35. Murphy J. T., Skuzeski J. T., Lund E., Steinberg T. H., Burgess R. R., Dahlberg J. E. Functional elements of the human U1 RNA promoter. Identification of five separate regions required for efficient transcription and template competition. J Biol Chem. 1987 Feb 5;262(4):1795–1803. [PubMed] [Google Scholar]
  36. Murphy S., Yoon J. B., Gerster T., Roeder R. G. Oct-1 and Oct-2 potentiate functional interactions of a transcription factor with the proximal sequence element of small nuclear RNA genes. Mol Cell Biol. 1992 Jul;12(7):3247–3261. doi: 10.1128/mcb.12.7.3247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Roebuck K. A., Szeto D. P., Green K. P., Fan Q. N., Stumph W. E. Octamer and SPH motifs in the U1 enhancer cooperate to activate U1 RNA gene expression. Mol Cell Biol. 1990 Jan;10(1):341–352. doi: 10.1128/mcb.10.1.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ross J. A precursor of globin messenger RNA. J Mol Biol. 1976 Sep 15;106(2):403–420. doi: 10.1016/0022-2836(76)90093-0. [DOI] [PubMed] [Google Scholar]
  39. Sadowski C. L., Henry R. W., Lobo S. M., Hernandez N. Targeting TBP to a non-TATA box cis-regulatory element: a TBP-containing complex activates transcription from snRNA promoters through the PSE. Genes Dev. 1993 Aug;7(8):1535–1548. doi: 10.1101/gad.7.8.1535. [DOI] [PubMed] [Google Scholar]
  40. Santiago C., Marzluff W. F. Expression of the U1 RNA gene repeat during early sea urchin development: evidence for a switch in U1 RNA genes during development. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2572–2576. doi: 10.1073/pnas.86.8.2572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Skuzeski J. M., Lund E., Murphy J. T., Steinberg T. H., Burgess R. R., Dahlberg J. E. Synthesis of human U1 RNA. II. Identification of two regions of the promoter essential for transcription initiation at position +1. J Biol Chem. 1984 Jul 10;259(13):8345–8352. [PubMed] [Google Scholar]
  42. Sánchez A., Jones W. K., Gulick J., Doetschman T., Robbins J. Myosin heavy chain gene expression in mouse embryoid bodies. An in vitro developmental study. J Biol Chem. 1991 Nov 25;266(33):22419–22426. [PubMed] [Google Scholar]
  43. Tanaka M., Grossniklaus U., Herr W., Hernandez N. Activation of the U2 snRNA promoter by the octamer motif defines a new class of RNA polymerase II enhancer elements. Genes Dev. 1988 Dec;2(12B):1764–1778. doi: 10.1101/gad.2.12b.1764. [DOI] [PubMed] [Google Scholar]
  44. Thomas K. R., Capecchi M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987 Nov 6;51(3):503–512. doi: 10.1016/0092-8674(87)90646-5. [DOI] [PubMed] [Google Scholar]
  45. Weller P., Bark C., Janson L., Pettersson U. Transcription analysis of a human U4C gene: involvement of transcription factors novel to snRNA gene expression. Genes Dev. 1988 Nov;2(11):1389–1399. doi: 10.1101/gad.2.11.1389. [DOI] [PubMed] [Google Scholar]
  46. Yoon J. B., Murphy S., Bai L., Wang Z., Roeder R. G. Proximal sequence element-binding transcription factor (PTF) is a multisubunit complex required for transcription of both RNA polymerase II- and RNA polymerase III-dependent small nuclear RNA genes. Mol Cell Biol. 1995 Apr;15(4):2019–2027. doi: 10.1128/mcb.15.4.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES