Nuclear matrix protein SMAR1 represses HIV-1 LTR mediated transcription through chromatin remodeling.
Nuclear Matrix and MARs have been implicated in the transcriptional regulation of host as well as viral genes but their precise role in HIV-1 transcription remains unclear. Here, we show that >98% of HIV sequences contain consensus MAR element in their promoter. We show that SMAR1 binds to the LTR MAR and reinforces transcriptional silencing by tethering the LTR MAR to nuclear matrix. SMAR1 associated HDAC1-mSin3 corepressor complex is dislodged from the LTR upon cellular activation by PMA/TNFalpha leading to an increase in the acetylation and a reduction in the trimethylation of histones, associated with the recruitment of RNA Polymerase II on the LTR. Overexpression of SMAR1 lead to reduction in LTR mediated transcription, both in a Tat dependent and independent manner, resulting in a decreased virion production. These results demonstrate the role of SMAR1 in regulating viral transcription by alternative compartmentalization of LTR between the nuclear matrix and chromatin.
National Centre for Cell science, University of Pune Campus, Ganeshkhind, Pune 411007, Maharashtra, India.
Kadreppa
K
Sreenath
Lakshminarasimhan
L
Pavithra
Sandeep
S
Singh
Surajit
S
Sinha
Prasanta K
PK
Dash
Nagadenahalli B
NB
Siddappa
Udaykumar
U
Ranga
Debashis
D
Mitra
Samit
S
Chattopadhyay
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D016384:Consensus Sequence; D015342:DNA Probes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D045170:Matrix Attachment Regions; D008954:Models, Biological; D015530:Nuclear Matrix / Q000378:metabolism / Q000821:virology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic
C417914:BANP protein, human; D018797:Cell Cycle Proteins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering