Negative elongation factor NELF represses human immunodeficiency virus transcription by pausing the RNA polymerase II complex

Zhiqiang Zhang, Alicia Klatt, David S. Gilmour, Andrew J. Henderson

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV) transcription requires virally encoded Tat and the P-TEFb protein complex, which together associate with the Tat-activating region, a structured region in the nascent transcript. P-TEFb phosphorylates proteins in the transcription elongation complex, including RNA polymerase II (pol II), to stimulate elongation and to overcome premature termination. However, the status of the elongation complex on the HIV long terminal repeat (LTR) in a repressed state is not known. Chromatin immunoprecipitation demonstrated that NELF, a negative transcription elongation factor, was associated with the LTR. Depleting NELF increased processive HIV transcription and replication. Mapping pol II on the LTR showed that pol II was paused and that NELF depletion released pol II. Decreasing NELF also correlated with displacement of a positioned nucleosome and increased acetylation of histone H4, suggesting coupling of transcription elongation and chromatin remodeling. Previous work has indicated that the Tat-activating region plays a critical role in regulating transcription from the LTR. Our results reveal an earlier stage, mediated by NELF, when repression occurs at the HIV LTR.

Original languageEnglish (US)
Pages (from-to)16981-16988
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number23
DOIs
StatePublished - Jun 8 2007

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Terminal Repeat Sequences
RNA Polymerase II
Positive Transcriptional Elongation Factor B
Transcription
Viruses
HIV Long Terminal Repeat
HIV
Elongation
Chromatin Assembly and Disassembly
Nucleosomes
Chromatin Immunoprecipitation
Acetylation
Virus Replication
Histones
Chromatin
Proteins
Transcription Factors
Peptide Elongation Factors
negative elongation factor

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Negative elongation factor NELF represses human immunodeficiency virus transcription by pausing the RNA polymerase II complex",
abstract = "Human immunodeficiency virus (HIV) transcription requires virally encoded Tat and the P-TEFb protein complex, which together associate with the Tat-activating region, a structured region in the nascent transcript. P-TEFb phosphorylates proteins in the transcription elongation complex, including RNA polymerase II (pol II), to stimulate elongation and to overcome premature termination. However, the status of the elongation complex on the HIV long terminal repeat (LTR) in a repressed state is not known. Chromatin immunoprecipitation demonstrated that NELF, a negative transcription elongation factor, was associated with the LTR. Depleting NELF increased processive HIV transcription and replication. Mapping pol II on the LTR showed that pol II was paused and that NELF depletion released pol II. Decreasing NELF also correlated with displacement of a positioned nucleosome and increased acetylation of histone H4, suggesting coupling of transcription elongation and chromatin remodeling. Previous work has indicated that the Tat-activating region plays a critical role in regulating transcription from the LTR. Our results reveal an earlier stage, mediated by NELF, when repression occurs at the HIV LTR.",
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Negative elongation factor NELF represses human immunodeficiency virus transcription by pausing the RNA polymerase II complex. / Zhang, Zhiqiang; Klatt, Alicia; Gilmour, David S.; Henderson, Andrew J.

In: Journal of Biological Chemistry, Vol. 282, No. 23, 08.06.2007, p. 16981-16988.

Research output: Contribution to journalArticle

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