Phospho-site mutants of the RNA Polymerase II C-terminal domain alter subtelomeric gene expression and chromatin modification state in fission yeast.

Autor: Inada M; Biology Department, Ithaca College, Ithaca, NY 14850, USA minada@ithaca.edu., Nichols RJ; Biology Department, Ithaca College, Ithaca, NY 14850, USA., Parsa JY; Department of Biochemistry and Biophysics, UCSF, San Francisco, CA 94158, USA., Homer CM; Department of Biochemistry and Biophysics, UCSF, San Francisco, CA 94158, USA., Benn RA; Biology Department, Ithaca College, Ithaca, NY 14850, USA., Hoxie RS; Biology Department, Ithaca College, Ithaca, NY 14850, USA., Madhani HD; Department of Biochemistry and Biophysics, UCSF, San Francisco, CA 94158, USA., Shuman S; Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA., Schwer B; Department of Microbiology, Weill Cornell Medical College, New York, NY 10065, USA., Pleiss JA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA jpleiss@cornell.edu.
Jazyk: angličtina
Zdroj: Nucleic acids research [Nucleic Acids Res] 2016 Nov 02; Vol. 44 (19), pp. 9180-9189. Date of Electronic Publication: 2016 Jul 08.
DOI: 10.1093/nar/gkw603
Abstrakt: Eukaryotic gene expression requires that RNA Polymerase II (RNAP II) gain access to DNA in the context of chromatin. The C-terminal domain (CTD) of RNAP II recruits chromatin modifying enzymes to promoters, allowing for transcription initiation or repression. Specific CTD phosphorylation marks facilitate recruitment of chromatin modifiers, transcriptional regulators, and RNA processing factors during the transcription cycle. However, the readable code for recruiting such factors is still not fully defined and how CTD modifications affect related families of genes or regional gene expression is not well understood. Here, we examine the effects of manipulating the Y 1 S 2 P 3 T 4 S 5 P 6 S 7 heptapeptide repeat of the CTD of RNAP II in Schizosaccharomyces pombe by substituting non-phosphorylatable alanines for Ser2 and/or Ser7 and the phosphomimetic glutamic acid for Ser7. Global gene expression analyses were conducted using splicing-sensitive microarrays and validated via RT-qPCR. The CTD mutations did not affect pre-mRNA splicing or snRNA levels. Rather, the data revealed upregulation of subtelomeric genes and alteration of the repressive histone H3 lysine 9 methylation (H3K9me) landscape. The data further indicate that H3K9me and expression status are not fully correlated, suggestive of CTD-dependent subtelomeric repression mechansims that act independently of H3K9me levels.
(© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze: MEDLINE
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