From: Subject: Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications -- Nathan et al., 10.1101/gad.1404206 -- Genes and Development Date: Sat, 15 Apr 2006 11:41:46 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0063_01C66081.93330580" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2180 This is a multi-part message in MIME format. ------=_NextPart_000_0063_01C66081.93330580 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.genesdev.org/cgi/content/abstract/gad.1404206v1?ijkey=7e4f9550eac2b74dbc2ece1bc06ac4380d4741e0&keytype2=tf_ipsecsha Histone sumoylation is a negative regulator in = Saccharomyces cerevisiae and shows dynamic interplay with = positive-acting histone modifications -- Nathan et al., = 10.1101/gad.1404206 -- Genes and Development
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Published online=20 before print April 5, 2006
Genes and=20 Development, DOI: 10.1101/gad.1404206
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3D""=20 Articles by Nathan, D. =
3D""=20 Articles by Berger, S. L.=20

Histone sumoylation is a negative regulator in Saccharomyces=20 cerevisiae and shows dynamic interplay with positive-acting histone=20 modifications

Dafna Nathan1,5, Kristin = Ingvarsdottir1,5, David E. = Sterner1,6, Gwendolyn R.=20 Bylebyl2, Milos Dokmanovic4,=20 Jean A. Dorsey1, Kelly A.=20 Whelan1, Mihajlo Krsmanovic4,=20 William S. Lane3, Pamela B.=20 Meluh4, Erica S. Johnson2 and=20 Shelley L. Berger1,7=20

1 Gene Expression and Regulation Program, The Wistar = Institute,=20 Philadelphia, Pennsylvania 19104, USA; 2 Department of = Biochemistry=20 and Molecular Biology, Thomas Jefferson University, Philadelphia, = Pennsylvania=20 10107, USA; 3 Microchemistry and Proteomics Analysis = Facility,=20 Harvard University, Cambridge, Massachusetts 02138, USA; 4 = Molecular=20 Biology and Genetics, Johns Hopkins University School of Medicine, = Baltimore,=20 Maryland 21205, USA=20

Covalent histone post-translational modifications such as = acetylation, methylation, phosphorylation, and ubiquitylation = play=20 pivotal roles in regulating many cellular processes, = including=20 transcription, response to DNA damage, and epigenetic = control.=20 Although positive-acting post-translational modifications = have been=20 studied in Saccharomyces cerevisiae, histone = modifications=20 that are associated with transcriptional repression have not = been=20 shown to occur in this yeast. Here, we provide evidence that = histone=20 sumoylation negatively regulates transcription in S.=20 cerevisiae. We show that all four core histones are = sumoylated=20 and identify specific sites of sumoylation in histones H2A, = H2B, and=20 H4. We demonstrate that histone sumoylation sites are = involved=20 directly in transcriptional repression. Further, while = histone=20 sumoylation occurs at all loci tested throughout the genome, = slightly=20 higher levels occur proximal to telomeres. We observe a = dynamic=20 interplay between histone sumoylation and either acetylation = or=20 ubiquitylation, where sumoylation serves as a potential block = to=20 these activating modifications. These results indicate that=20 sumoylation is the first negative histone modification to be=20 identified in S. cerevisiae and further suggest that=20 sumoylation may serve as a general dynamic mark to oppose=20 transcription.

[Keywords: Histone post-translational modifications; = sumoylation;=20 transcription regulation; telomeric silencing]

Received August 23, 2005; revised version accepted February 8, 2006.

5 These authors = contributed=20 equally to this work.

6 Current address: = Progenra, Inc.,=20 271A Great Valley Parkway, Malvern, PA 19355, USA. =

7 Corresponding = author.

E-MAIL berger{at}wistar.upenn.edu ; FAX (215) 898-0663.

Article published online ahead of = print. Article=20 and publication date are at http://www.g= enesdev.org/cgi/doi/10.1101/gad.1404206=20





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