Interplay of Chromatin Modifiers on a Short Basic Patch of Histone H4 Tail Defines the Boundary of Telomeric Heterochromatin

Mohammed Altaf, Rhea T. Utley, Nicolas Lacoste, Song Tan, Scott D. Briggs, Jacques Côté

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Dot1 (Disruptor of telomeric silencing-1) is a histone H3 lysine 79 methyltransferase that contributes to the establishment of heterochromatin boundary and has been linked to transcription elongation. We found that histone H4 N-terminal domain, unlike other histone tails, interacts with Dot1 and is essential for H3 K79 methylation. Furthermore, we show that the heterochromatin protein Sir3 inhibits Dot1-mediated methylation and that this inhibition is dependent on lysine 16 of H4. Sir3 and Dot1 bind the same short basic patch of histone H4 tail, and Sir3 also associates with the residues surrounding H3 K79 in a methylation-sensitive manner. Thus, Sir3 and Dot1 compete for the same molecular target on chromatin. ChIP analyses support a model in which acetylation of H4 lysine 16 displaces Sir3, allowing Dot1 to bind and methylate H3 lysine 79, which in turn further blocks Sir3 binding/spreading. This draws a detailed picture of the succession of molecular events occurring during the establishment of telomeric heterochromatin boundaries.

Original languageEnglish (US)
Pages (from-to)1002-1014
Number of pages13
JournalMolecular cell
Volume28
Issue number6
DOIs
StatePublished - Dec 28 2007

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Heterochromatin
Histones
Lysine
Chromatin
Methylation
Methyltransferases
Acetylation
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Altaf, Mohammed ; Utley, Rhea T. ; Lacoste, Nicolas ; Tan, Song ; Briggs, Scott D. ; Côté, Jacques. / Interplay of Chromatin Modifiers on a Short Basic Patch of Histone H4 Tail Defines the Boundary of Telomeric Heterochromatin. In: Molecular cell. 2007 ; Vol. 28, No. 6. pp. 1002-1014.
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Interplay of Chromatin Modifiers on a Short Basic Patch of Histone H4 Tail Defines the Boundary of Telomeric Heterochromatin. / Altaf, Mohammed; Utley, Rhea T.; Lacoste, Nicolas; Tan, Song; Briggs, Scott D.; Côté, Jacques.

In: Molecular cell, Vol. 28, No. 6, 28.12.2007, p. 1002-1014.

Research output: Contribution to journalArticle

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