NDLI: Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription

Content Provider	Journal of Biological Chemistry (JBC)
Author	Natarajan, Malini Lester, Gillian M. Schiralli Lee, Chanhyo Missra, Anamika Wasserman, Gregory A. Steffen, Martin Gilmour, David S. Henderson, Andrew J.
Abstract	A barrier to eradicating HIV infection is targeting and eliminating latently infected cells. Events that contribute to HIV transcriptional latency include repressive chromatin structure, transcriptional interference, the inability of Tat to recruit positive transcription factor b, and poor processivity of RNA polymerase II (RNAP II). In this study, we investigated mechanisms by which negative elongation factor (NELF) establishes and maintains HIV latency. Negative elongation factor (NELF) induces RNAP II promoter proximal pausing and limits provirus expression in HIV-infected primary CD4+ T cells. Decreasing NELF expression overcomes RNAP II pausing to enhance HIV transcription elongation in infected primary T cells, demonstrating the importance of pausing in repressing HIV transcription. We also show that RNAP II pausing is coupled to premature transcription termination and chromatin remodeling. NELF interacts with Pcf11, a transcription termination factor, and diminishing Pcf11 in primary CD4+ T cells induces HIV transcription elongation. In addition, we identify NCoR1-GPS2-HDAC3 as a NELF-interacting corepressor complex that is associated with repressed HIV long terminal repeats. We propose a model in which NELF recruits Pcf11 and NCoR1-GPS2-HDAC3 to paused RNAP II, reinforcing repression of HIV transcription and establishing a critical checkpoint for HIV transcription and latency.
Related Links	http://www.jbc.org/content/288/36/25995.abstract
Ending Page	26003
Starting Page	25995
Page Count	9
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	36
Volume Number	288
DOI	10.1074/jbc.M113.496489
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2013-09-06
Access Restriction	Open
Subject Keyword	HIV RNA Polymerase II Transcription Elongation Factors Transcription Regulation Transcription Repressor Microbiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription*

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Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription

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