Question

17. Which histone is required to compact the “beads on a string” chromatin into higher-order chromatin structures such as the 30 nm fiber?

18. Certain lysine amino acids (K’s) in the core histone tail can be acetylated. How would this chemical modification of the nucleosome affect the transcription of a gene?

19. Certain protein/protein complexes do not bind DNA, but regulate processes such as transcription and replication. These proteins can associate with the chromatin by recognizing chemical modifications in the core histone tails of the nucleosome. This process represents the “histone code”. Separately, a protein that folds into its three-dimensional functional structures can have different domains with different functions. Assume that a certain protein that increases transcription does not recognize a specific DNA sequence, but rather associates with acetylated lysine amino acids in the histone tails. What domain in this protein would allow it to associate with these acetylated lysine amino acids?

Answer 1

17. Chromosomal DNA is packaged inside microscopic nuclei with the help of histones(H1). These are positively-charged proteins that strongly adhere to negatively-charged DNA and form complexes called nucleosomes. Each nuclesome is composed of DNA wound 1.65 times around eight histone proteins. Nucleosomes fold up to form a 30-nanometer chromatin fiber, which forms loops averaging 300 nanometers in length. The 300 nm fibers are compressed and folded to produce a 250 nm-wide fiber, which is tightly coiled into the chromatid of a chromosome.

18.  acetyllysine residues on histone tails form binding sites for bromodomains on various proteins suggests a quite different function (reviewed in Dyson et al. [2001], Loyola and Almouzni [2004], Yang [2004], and Zeng and Zhou [2002]). This indicates that acetylation, akin to many protein phosphorylation events, creates a new binding surface to recruit other proteins to the nucleosome. It is worth noting that, in charge neutralization models, acetylation of multiple or all lysine residues upon a single histone tail (hyperacetylation) would produce a stronger effect. By contrast, in bromodomain-recruitment models in which adjacent amino acids determine specificity, a single lysine residue on a histone tail is relevant, and hyperacetylation of the entire tail would not be expected to contribute further to recruitment. It is possible that for a specific lysine residue, both functional modalities of acetylation may be physiologically relevant and apply in different circumstances, as recently suggested from in vitro studies of H4-K16 acetylation .

19. Adenoviral E1A-associated protein of 300kDa (p300) and the CREB-binding protein (CBP) make up the next family of HATs.This family of HATs contain HAT domains that are approximately 500 residues long and contain bromodomains as well as three cysteine-histidine rich domains that help with protein interactions.These HATs are known to acetylate all of the histone subunits in the nucleosome. They also have the ability to acetylate and mediate non-histone proteins involved in transcription and are also involved in the cell cycle, differentiation and apoptosis