Hypersensitive sites, chromatin

Structural studies of the chromatin organization of integrated HlV-1 have identified two DNase 1-Hypersensitive Sites (HS4 and HS7) outside of the promoter/enhancer region in U3, that were likely to play a role in controlling viral transcription by virtue of their accessibility in chromatin (Fig. la and lb) (Verdin, 1991). 

Analysis of the chromatin organization of integrated HIV-1 identified a single major nuclease-hypersensitive site in the 8 kb region located between the two LTRs (Verdin, 1991 Van Lint et al, 1994). This hypersensitive site, centered around nt... 

Van Lint C, (2000) Role of chromatin in HIV-1 transcriptional regulation. Adv Pharmacol 48 121-160 Verdin E (1991) DNase I-hypersensitive sites are associated with both long terminal repeats and with the intragenic enhancer of integrated human immunodeficiency vims type 1. J Virol 65 6790-6799... 

Many hypersensitive sites correspond to binding sites for known regulatory proteins, and the relative absence of nucleosomes in these regions may allow the binding of these proteins. Nucleosomes are entirely absent in some regions that are very active in transcription, such as the rRNA genes. Transcriptionally active chromatin tends to be deficient in histone HI, which binds to the linker DNA between nucleosome particles. 

Transcriptional control in eukaryotes can be accomplished at several levels. Chromatin structure can control transcription. The formation of so-called hypersensitive sites (sites where the DNA is not bound into nucleosomes) allows protein factors and RNA polymerase to access the DNA. This is necessary for transcription to occur, but hypersensitive sites are not enough. The removal of histone HI allows transcription to occur from a chromatin domain. Some protein factors (for example, TBF) may be bound to a promoter region even if the gene is not being transcribed. TBF also is necessary but not sufficient for transcription. 

Other recent results also suggest that the interaction of the receptor-T3 complex with the chromatin alters the local chromatin structure [59], This was shown by treating the chromatin prepared from cells exposed to T3 with DNAse I three hypersensitive sites were identified in the region spanning the transcriptional initiation site from -200 to +150. The first site was in the first intron of the gene. The... 

S.C. Elgin. 1981. DNAase I-hypersensitive sites of chromatin Cell 27 413-415. (PubMed)... 

Bonven, B. J., Gocke, E., and Westergaard, O. (1985) A high affinity topoisomerase I binding sequence is clustered at DNAase I hypersensitive sites in Tet-rahymena R-chromatin. Cell 41, 541-551. 

The number and locations of hypersensitive sites in the chromatin fiber are specific to individual genes and also vary depending on whether the gene is active or merely competent. 

The DNAase-hypersensitive sites are small and dispersed throughout the chromatin they are interpreted as being due to the absence of histones or nucleosomes. Often, the binding of other proteins can be detected in the hypersensitive sites, using more sophisticated "footprinting" techniques. There is growing evidence for the existence of multi-subunit complexes of proteins bound at hypersensitive sites which may control the initiation of transcription. 

Hypersensitive site A site on chromatin that has a sensitivity to DNAase-1 similar to that of free DNA. 

Rohdewohld H., Weinher H., Reik W., Jaenisch R., Breindl M. (1987). Retrovirus integration and chromatine structure Moloney murine leukemia proviral integation sites map near DNase I-hypersensitive sites. J. Virol. 61 336-343. 

Vijaya S., Steffen D.L., Kozak C., Robinson H.L. (1986). Acceptor sites for retroviral integrations map near DNA I-hypersensitive sites in chromatin. J. Virol. 60 683-692. 

Gross, D.S. Garrard, W.T. (1988). Nuclease hypersensitive sites in chromatin. Annu. Rev. Biochem., 57, 159-97. 

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