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Transcriptional inhibition of genes with severe histone H3 hypoacetylation in the coding region

Arnold Kristjuhan, Jane Walker, Noriyuki Suka, Michael Grunstein, Douglas Roberts, Bradley R. Cairns, Jesper Q. Svejstrup*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

106 Citations (Scopus)

Abstract

Changes in histone acetylation at promoters correlate with transcriptional activation and repression, but whether acetylation of histones in the coding region of genes is important for transcription is less clear. Here, we show that cells lacking the histone acetyltransferases Gcn5 and Elp3 have widespread and severe histone H3 hypoacetylation in chromatin. Surprisingly, severe hypoacetylation in the promoter does not invariably affect the ability of TBP to bind the TATA element, or transcription of the gene. By contrast, similar hypoacetylation of the coding region correlates with inhibition of transcription, and inhibition correlates better with the overall charge of the histone H3 tail than with hypoacetylation of specific lysine residues. These data provide insights into the effects of histone H3 hypoacetylation in vivo and underscore the importance of the overall charge of the histone tail for transcription.

Original languageEnglish
JournalMolecular Cell
Volume10
Issue number4
Pages (from-to)925-933
Number of pages9
ISSN1097-2765
DOIs
Publication statusPublished - 1 Oct 2002
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from Cancer Research UK and the EU (HPRN-CT-2000-00087) to J.Q.S., by Public Health Service Grant of the National Institutes of Health (NIH) GM23674 to M.G., and by Public Health Service Grant of the NIH GM60415 and support of core facilities by NIH (CA24014) to B.R.C. We thank Kevin Struhl and Alain Verreault for gifts of yeast strains and antibody, respectively. Tomas Lindahl and Alain Verreault are thanked for comments on the manuscript. Cancer Research UK London Research Institute comprises the Lincoln's Inn Fields and Clare Hall Laboratories of the former Imperial Cancer Research Fund following the merger of the ICRF with the Cancer Research Campaign in February 2002.

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