Nuclear matrix protein SMAR1 represses HIV-1 LTR mediated transcription through chromatin remodeling.

Abstract:

: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.

journal_name

Virology

journal_title

Virology

authors

Sreenath K,Pavithra L,Singh S,Sinha S,Dash PK,Siddappa NB,Ranga U,Mitra D,Chattopadhyay S

doi

10.1016/j.virol.2010.01.017

subject

Has Abstract

pub_date

2010-04-25 00:00:00

pages

76-85

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(10)00034-6

journal_volume

400

pub_type

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