Promoter site histone

The answer is a. (Murray, pp 435-451. Scriver, pp 3-45. Sack, pp 1-40. Wilson, pp 101-120.) In mammals, RNA polymerase binds to promoter sites upstream from the start site. These include the TATA box (TATAAT), the CAAT box, and the GC box. DNA primase and helicase are involved in DNA replication and do not bind specifically to sequences upstream of genes. Restriction endonucleases recognize specific sequences in double-helical DNA and cleave both strands. Histones nonspecifically bind to chromosomal DNA and constitute about half the mass of mammalian chromosomes. 

Vassen L, Fiolka K, Moroy T (2006). Gfilb alters histone methylation at target gene promoters and sites of gamma-satellite containing heterochromatin. EMBO J 25 2409-2419 Verdel A, Moazed D (2005) RNAi-directed assembly of heterochromatin in fission yeast. EEBS Lett 579(26) 5872-5878... 

He G, Margolis DM (2002) Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HlV-1) by the HlV-1 repressor YYl and HlV-1 activator Tat. Mol Cell Biol 22 2965-2973 Henderson AJ, Calame KL (1997) CCAAT/enhancer binding protein (C/EBP) sites are required for HlV-1 replication in primary macrophages but not CD4-t T cells. Proc Natl Acad Sci USA 94 8714-8719... 

Smithgall MD, Wong JG, Critchett KE, Haffar OK (1996) E--7 up-regulates HIV-1 replication in naturally infected peripheral blood mononuclear cells. J Iimnunol 156 2324—2330 Sowa Y, Orita T, Minamikawa S, Nakano K, Mizuno T, Nomura H, Sakai T (1997) Histone deacetylase inhibitor activates the WAEl/Cipl gene promoter through the Spl sites. Biochem Biophys Res Commun 241 142-150... 

Van Lint C, Emiliani S, Ott M, Verdin E (1996a) Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J 15 1112-1120 Van Lint C, Emiliani S, Verdin E (1996b) The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr 5 245-53 Van Lint C, Amelia CA, Emiliani S, John M, Jie T, Verdin E (1997) Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for vims infectivity. J Virol 71 6113-6127... 

The specific regulatory role of HI documented for the Xenopus 5S RNA gene points to the importance of AT-rich tracts in the genome as potential sites of strong and preferential HI binding. Indeed, it has been shown that histone HI is probably involved in the repression of the murine /1-interferon promoter by binding to its upstream AT-rich region [143]. 

The model of Fig. IB is taken from a review by van Holde et al. [3] which I refer to as the disruptive model. In this model the polymerase causes conditions (step A) which promote not only the displacement of the entry site H2A, H2B dimer from DNA, but also from the H3, H4 tetramer (step B). As a result of this disruption, the polymerase is free to transcribe through the tetramer alone without a general displacement from its associated DNA (step C). The H2A, H2B dimer is now free to reassociate to the vacated entry site (step D) to re-establish contacts with both the DNA and the H3, H4 tetramer. As transcription proceeds into the exit site H2A, H2B dimer, these proteins are now displaced from both the DNA and the H3, H4 tetramer in a similar manner as the entry site H2A, H2B dimer (step E). A positive feature with regard to this model is that by displacement of H2A, H2B, the polymerase is able to transcribe the DNA with half the histones displaced prior to transcription. Therefore both models, spooling and disruptive , describe mechanisms which would favorably enhance the process of transcription. Support for the disruptive model comes from the substantial in vivo information which suggests that nucleosomes undergo substantial disruption during transcription, as was described in the previous section. Of particular note are those observations which indicate that a discrete population of H2A, H2B... 

Flavone has been shown to be effective at 170 /iM concentration to inhibit HDAC-1 activity, and also to induce histone H3 acetylation in NB4 APL cell lines. Flavone s mechanism of HDAC inhibition is currently unknown, but it has been proposed that similar to the inhibitors of kinases, it might occupy the exit channel or an alternative, shallow binding site found in HDAC with possible effects of causing allosteric modulation. This blockage or allosteric modulation would promote inhibition. ... 

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