Justin M O'Sullivan ^{1, 3}, Sue Mei Tan-Wong ^{1, 3}, Antonin Morillon ^{2, 3}, Barbara Lee ¹, Joel Coles ¹,
Jane Mellor ² and Nick J Proudfoot ¹

¹ Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK.
² Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.

³ These authors contributed equally to this work.

Correspondence should be addressed to Nick J Proudfoot:   nicholas.proudfoot@path.ox.ac.uk 

Mechanistic analysis of transcriptional initiation and termination by RNA polymerase II (PolII) indicates that some factors are common to both processes [1, 2]. Here we show that two long genes of Saccharomyces cerevisiae, FMP27 and SEN1, exist in a looped conformation, effectively bringing together their promoter and terminator regions. We also show that PolII is located at both ends of FMP27 when this gene is transcribed from a GAL1 promoter under induced and noninduced conditions. Under these conditions, the C-terminal domain of the large subunit of PolII is phosphorylated at Ser5. Notably, inactivation of Kin28p causes a loss of both Ser5 phosphorylation and the loop conformation. These data suggest that gene loops are involved in the early stages of transcriptional activation. They also predict a previously unknown structural dimension to gene regulation, in which both ends of the transcription unit are defined before and during the transcription cycle.

Supplementary Information:
http://www.nature.com/ng/journal/v36/n9/suppinfo/ng1411_S1.html

Additional References:

1. Frenster JH, and Hovsepian JA, "Ultrastructure  of Closed Loops within Euchromatin of Isolated Lymphocyte Nuclei".

2. Chambeyron S,  and Bickmore WA, "Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription",Genes & Development, vol. 18: no. 10, pp. 1119-1130 (May 15, 2004).

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4. Frenster JH, Allfrey VG, and Mirsky AE, "Metabolism and Morphology of Ribonucleoprotein Particles from the Cell Nucleus of Lymphocytes", Proc. Natl. Acad. Sci. U.S.A. vol. 46: no. 4, pp. 432-444 (April, 1960).

5. Frenster JH, Allfrey VG, and Mirsky AE, "Repressed and Active Chromatin Isolated from Interphase Lymphocytes", Proc. Natl. Acad. Sci., U.S.A. vol. 50, no. 6, pp. 1026-1032 (December, 1963).

6. Parada LA, McQueen PG,  and Misteli T, "Tissue-specific spatial organization of genomes", Genome Biology, vol. 5, no. 7, r44 (June 21, 2004).

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8. Frenster JH, Nakatsu SL, and Masek MA, "Ultrastructural Probes of DNA Templates within Human Bone Marrow and Lymph Node Cells", in: "Advances in Cell and Molecular Biology", vol. 3, pp. 1-19 (1974), ed. DuPraw EJ, New York: Academic Press.

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11. Fransz P, de Jong JH, Lysak M, Castiglione MR, and Schubert I, " Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate", Proc. Natl. Acad. Sci., U.S.A., vol. 99, no. 22, pp. 14584-14589 (October 29, 2002).

12. Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, and Fraser P, "Active genes dynamically colocalize to shared sites of ongoing transcription".

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