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Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus

The putative model of HMGA1-mediated activation of transcription. The putativemechanism of transcriptional regulation by HMGA1: HMGA1 promotes chromatinreorganization by exposing DNA sites for transcription initiation factors.A – HMGA1 competes with histone H1 by replacing it.B – chromatin decompactization usingchromatin-remodeling complexes (CRCs). Binding of CRC to chromatin increaseswhen it interacts with HMGA1. C – release of DNA forbinding to transcription factors. D – initiation oftranscription: HMGA1 can interact with transcription factors (TFs) byrecruiting them to the promoter [62].
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Figure 6: The putative model of HMGA1-mediated activation of transcription. The putativemechanism of transcriptional regulation by HMGA1: HMGA1 promotes chromatinreorganization by exposing DNA sites for transcription initiation factors.A – HMGA1 competes with histone H1 by replacing it.B – chromatin decompactization usingchromatin-remodeling complexes (CRCs). Binding of CRC to chromatin increaseswhen it interacts with HMGA1. C – release of DNA forbinding to transcription factors. D – initiation oftranscription: HMGA1 can interact with transcription factors (TFs) byrecruiting them to the promoter [62].

Mentions: Actually, all the high-mobility group proteins are capable of binding both DNAand proteins, which allows them to get involved in a large number of processes[64]. Alteration in the chromatinstructure induced by HMGA binding either stimulates or represses suchDNA-dependent processes as transcription, replication, and DNA-repair. HMGA1 isconsidered to be an architectural transcription factor, and this emphasizes itsrole in the organization of multiprotein complexes bound to the promoter[62-64].The ability of HMGA1 to interact with core histones and displace the linkerhistone H1 from DNA results in chromatin reorganization and exposure oftranscription factor binding sites(Fig. 6). HMGA1plays a crucial role in the regulation of enhanceosome assembly or disassembly, thusaffecting transcription. It has been repeatedly demonstrated that HMGA1directly interacts with other chromatin-re-modeling proteins and transcriptionfactors (Sp1, TFIID, NF-κB, ATF-2, SRF, Oct2, and c-Rel)[62, 63].The ability of HMGA1 to bend DNA upon binding probably facilitates spatial proximityof the enhancer and promoter regions of the genes.


Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

The putative model of HMGA1-mediated activation of transcription. The putativemechanism of transcriptional regulation by HMGA1: HMGA1 promotes chromatinreorganization by exposing DNA sites for transcription initiation factors.A – HMGA1 competes with histone H1 by replacing it.B – chromatin decompactization usingchromatin-remodeling complexes (CRCs). Binding of CRC to chromatin increaseswhen it interacts with HMGA1. C – release of DNA forbinding to transcription factors. D – initiation oftranscription: HMGA1 can interact with transcription factors (TFs) byrecruiting them to the promoter [62].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837570&req=5

Figure 6: The putative model of HMGA1-mediated activation of transcription. The putativemechanism of transcriptional regulation by HMGA1: HMGA1 promotes chromatinreorganization by exposing DNA sites for transcription initiation factors.A – HMGA1 competes with histone H1 by replacing it.B – chromatin decompactization usingchromatin-remodeling complexes (CRCs). Binding of CRC to chromatin increaseswhen it interacts with HMGA1. C – release of DNA forbinding to transcription factors. D – initiation oftranscription: HMGA1 can interact with transcription factors (TFs) byrecruiting them to the promoter [62].
Mentions: Actually, all the high-mobility group proteins are capable of binding both DNAand proteins, which allows them to get involved in a large number of processes[64]. Alteration in the chromatinstructure induced by HMGA binding either stimulates or represses suchDNA-dependent processes as transcription, replication, and DNA-repair. HMGA1 isconsidered to be an architectural transcription factor, and this emphasizes itsrole in the organization of multiprotein complexes bound to the promoter[62-64].The ability of HMGA1 to interact with core histones and displace the linkerhistone H1 from DNA results in chromatin reorganization and exposure oftranscription factor binding sites(Fig. 6). HMGA1plays a crucial role in the regulation of enhanceosome assembly or disassembly, thusaffecting transcription. It has been repeatedly demonstrated that HMGA1directly interacts with other chromatin-re-modeling proteins and transcriptionfactors (Sp1, TFIID, NF-κB, ATF-2, SRF, Oct2, and c-Rel)[62, 63].The ability of HMGA1 to bend DNA upon binding probably facilitates spatial proximityof the enhancer and promoter regions of the genes.

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus