Histone-DNA Interactions

The a-mGI motif operates primarily through the induced dipole of the a helices directed toward DNA phosphates (Fig. 13a) and was termed the paired element motif (PEM) [17], although paired ends of helices is more descriptive. The guanido group is restrained from binding deeply into the mGI by a threonine from another histone. This steric hindrance preserves the avidity of the histone core for DNA, but prevents overly strong binding that would disrupt the plasticity of the histone-DNA interaction. 

Jackson, V. (1990) In vivo studies on the dynamics of histone-DNA interaction evidence for nucleosome dissolution during replication and transcription and a low level of dissolution independent of both. Biochemistry. 29, 719-731. 

Regardless of the loeal or global nature of histone acetylation, how these two elfects alfect chromatin structure still remains an open question. As it will be discussed in Section 6.2, proving the initial hypothesis that histone acetylation weakens the histone-DNA interactions in a way that facilitates chromatin unfolding has not been that simple. 

Aoyagi, S., Narlikar, G., Zheng, C., Sif, S., Kingston, R.E., and Hayes, J.J. (2002) Nucleosome remodeling by the human SWI/SNF complex requires transient global disruption of histone-DNA interactions. Mol. Cell. Biol. 22, 3653-3662. 

Vibrational spectroscopy was used to study native chromatin as well as reconstituted DNA-histone complexes. IR (Liquier et al., 1979) and Raman spectra (Goodwin and Brahms, 1978 Savoie et al., 1985) show that the DNA in chromatin adopts a B type conformation. The important role adopted by the a helical parts of the histones in stabilizing the B conformation of histone-DNA complexes was demonstrated by IR (Taillandier et al., 1984b). Raman spectra of chromatin have made it possible to localize histone-DNA interactions in the minor groove and non-histone protein-DNA interactions in the major groove (Goodwin and Brahms, 1978). 

Histone chaperones bind histones and facilitate their proper deposition onto DNA by preventing nonspecific histone-DNA interactions (17). Two major histone chaperones are CAF-1 and NAP-1. CAF-1 localizes to the replication fork by binding PCNA and facilitates the deposition of histones H3 and H4 onto the newly synthesized DNA strands (18,19). Subsequently, NAP-1 facilitates the deposition of histones H2A and H2B to complete the nucleosome (20). Using in vitro nucleosome assembly and nuclease digestion mapping assays, it was shown that the periodic spacing of nucleosomes requires the function of ATP-dependent chromatin remodeling factors, such as the ACF/ISWI complex (16, 21). 

As discussed, histones are an integral part of nucleo-somes, the basic repeating structural unit of chromatin. The amino termini of histone proteins can be modified post-translationally by processes that include acetylation, methylation, phosphorylation, and ubiquination. Acetylation of the lysines on the amino termini of histones H3 and H4 by histone acetyltransferases decreases histone-DNA interaction and improves the accessibility of DNA to transcriptional activation. On the contrary, histone deacetylation by histone deacetylases promotes the formation of compact nucleo-somes, leading to repression of transcription. Histone deacetylation is in fact a key component to the assembly of heterochromatin, the transcriptionally inactive chromatin. Methylation of the ninth amino acid residue, lysine, on histone H3 generates a binding site for heterochromatin protein (HP 1) and thus is another key event in heterochromatin formation. Phosphorylation of the tenth amino acid, serine, on histone H3 is important for chromosome condensation and mitosis. 

Furthermore, the severe structural distortion of the DNA in the nucleosome is something of an Achilles heel, since it implies that this entire structure is amenable to disruption. We do not wish to create the impression that the nucleosome is intrinsically unstable—quite the contrary, an intact histone octamer can remain complexed with DNA under conditions of physiological pH and low ionic strength for very extended periods of time. Should the arrangement of the core histones within the nucleosome, or histone-DNA interactions themselves be altered, however, DNA will attempt to release topological and structural stress by recovering some B-form normalcy. This feature of the nucleosome is efficiently exploited in transcriptional control. 

FIGURE 7 (A) The histone dimers as they interact in the nucleosome. For simplicity, only one histone set is shown. (B) The nucleosome and locations of histone-DNA interactions. 

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