Chromatin structure changes

TABLE 28-2 Some Enzyme Complexes Catalyzing Chromatin Structural Changes Associated with Transcription... 

Poly(ADP-ribose) polymerase is activated by DNA strand breaks and this property is central to its regulatory role in cell metabolism. The enzyme is tightly bound to chromatin where it ADP-ribosylates chromosomal proteins including histones, nonhistones, and itself (automodification), and its activity influences and is influenced by chromatin structural changes. These properties point to a funda-... 

Burch BE, Weintraub H (1983) Temporal order of chromatin structural changes associated with activation of the major chicken vitellogenin gene. Cell 33 65-76... 

Finally, the binding of specific transcription factors to cognate DNA elements may result in disruption of nucleosomal structure. Many eukaryotic genes have multiple protein-binding DNA elements. The serial binding of transcription factors to these elements—in a combinatorial fashion—may either directly disrupt the structure of the nucleosome or prevent its re-formation or recruit, via protein-protein interactions, multiprotein coactivator complexes that have the ability to covalently modify or remodel nucleosomes. These reactions result in chromatin-level structural changes that in the end increase DNA accessibifity to other factors and the transcription machinery. 

The similarity of the various histone fibers is probably correlated with the similarity in the distribution of the amino acids in the sequences of the four core histones and reflects their function as the skeleton or backbone of chromatin. However, from the presence of a specific pattern of interactions of the core histones and the existence of histone variants and histone postsynthetic modifications, one can anticipate modulations in the basic general pattern of histone structure. In Section V, a possible mechanism for histone microheterogeneity influencing chromatin structure is suggested. Analogous to other assembly systems, small subunit modifications may be amplified to produce major changes in the assembled superstructure. 

In the previous paragraph changes occurring at the level of chromatin structure have been described. All these events cannot be considered from those taking place in the cytoplasm. Indeed, it is very likely that, albeit classical definition of apoptosis is based upon morphological criteria involving mainly the nucleus, cytoplasmic events are pivotal in determining the cellular fate after inadiation. 

Figure 4. In vitro reconstituted 30 nm chromatin fiber. Dynamic structural changes in the chromatin fiber in the absence (top) or presence (bottom) of linker histone HI with different NaCl concentration were observed by AFM. Nucleosomes were reconstituted on the 106 kb plasmid and then fixed in the buffer containing 50 mM (top left) or 100 mM NaCl (top right). Nucleosomes were well-spread in 50 mM NaCl but attached each other and partially aggregated in 100 mM NaCl. After the addition of histone HI, the thicker fibers were formed. The width of the fibers is 20nm in 50mM NaCl (bottom left) or 30 nm in lOOmM NaCl (bottom right)...

The absence of a transactivation-competent NF-kB heterodimer in the nucleus of latently infected resting memory CD4+ T cells could contribute to latency. Activation of the NF-kB pathway leading to migration of a transactivating heterodimer such as p50/p65 could allow viral reactivation. In the absence of induction, NF-kB p50-HDACl complexes constitutively bind the latent HIV-1 LTR (Williams et al, 2006). NF-kB p50 does not possess a transactivation domain. These p50-HDACl complexes induce histone deacetylation and repressive changes in chromatin structure of the HIV-1 LTR (Williams et al, 2006). Knockdown of p50 expression reduces HDACl binding to the latent HIV-1 LTR and induces RNA polymerase II recruitment (Williams et al, 2006). Concomitantly with HIV-1 transcriptional activation, the p65 subunit and different HATs are recruited to the viral promoter (Lusic et al, 2003 Thierry et al, 2004). 

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