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THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 288, NO. 36, pp. 25995?6003, September six, 2013 ?2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published inside the U.S.A.Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV TranscriptionReceived for publication, June 24, 2013, and in revised kind, July 23, 2013 Published, JBC Papers in Press, July 24, 2013, DOI 10.1074/jbc.M113.Malini Natarajan?,two, Gillian M. Schiralli Lester?, Chanhyo Lee? Anamika Missra? Gregory A. Wasserman , Martin Steffen, David. S. Gilmour? and Andrew J. NLRP3 Activator Purity & Documentation Henderson?three From the Immunology and Infectious Diseases, Integrated Biosciences Graduate Plan, Penn State University, University Park, Pennsylvania 16802, the �Departments of Medicine and Infectious Diseases, Microbiology, and Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 and the epartment of Biochemistry and Molecular Biology, Penn State University, University Park, PennsylvaniaBackground: Several mechanisms contribute to HIV latency, like NELF-mediated RNA polymerase II (RNAP II) pausing. Outcomes: Paused RNAP II recruits a transcription termination issue and a transcriptional corepressor complicated to the HIV promoter. Conclusion: Paused RNAP II couples premature transcription termination and chromatin remodeling to retain HIV latency. Significance: Paused RNAP II could be targeted to purge latent HIV infection. 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 good transcription aspect b, and poor processivity of RNA polymerase II (RNAP II). In this study, we investigated mechanisms by which damaging elongation issue (NELF) establishes and maintains HIV latency. Negative elongation aspect (NELF) induces RNAP II promoter proximal pausing and limits provirus expression in HIV-infected main CD4 T cells. Decreasing NELF e.