http://www.people.vcu.edu/~mreimers/SysBio/Li%20-%20Role%20of%20chromatin%20in%20transcription.pdf

The Role of Chromatin during Transcription

An important development in understanding the influence of chromatin on gene regulation has been the finding that DNA methylation and histone post-translational modifications lead to the recruitment of protein complexes that regulate transcription. Early interpretations of this phenomenon involved gene regulation reflecting predictive activating or repressing types of modification. However, further exploration reveals that transcription occurs against a backdrop of mixtures of complex modifications, which probably have several roles. Although such modifications were initially thought to be a simple code, a more likely model is of a sophisticated, nuanced chromatin 'language' in which different combinations of basic building blocks yield dynamic functional outcomes.

/pdf/the-complex-language-of-chromatin-regulation-during-116ycky1u0.pdf

The complex language of chromatin regulation during transcription

Histone acetylation regulates many cellular processes, and specific acetylation marks, either singly or in combination, produce distinct outcomes. For example, the acetylation pattern on newly synthesized histones is important for their assembly into nucleosomes by histone chaperones. Additionally, the degree of chromatin compaction and folding may be regulated by acetylation of histone H4 at lysine 16. Histone acetylation also regulates the formation of heterochromatin; deacetylation of H4 lysine 16 is important for spreading of heterochromatin components, whereas acetylation of this site serves as a barrier to this spreading. Finally, histone acetylation is critical for gene transcription, but recent results suggest that deacetylation of certain sites also plays an important role. There are many histone acetyltransferases (HATs) and deacetylases, with differing preferences for the various histone proteins and for specific sites on individual histones. Determining how these enzymes create distinc...

Functions of site-specific histone acetylation and deacetylation.

Cytosine methylation, a common form of DNA modification that antagonizes transcription, is found at transposons and repeats in vertebrates, plants and fungi. Here we have mapped DNA methylation in the entire Arabidopsis thaliana genome at high resolution. DNA methylation covers transposons and is present within a large fraction of A. thaliana genes. Methylation within genes is conspicuously biased away from gene ends, suggesting a dependence on RNA polymerase transit. Genic methylation is strongly influenced by transcription: moderately transcribed genes are most likely to be methylated, whereas genes at either extreme are least likely. In turn, transcription is influenced by methylation: short methylated genes are poorly expressed, and loss of methylation in the body of a gene leads to enhanced transcription. Our results indicate that genic transcription and DNA methylation are closely interwoven processes.

Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription

Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription.

Previous studies have suggested that transcription elongation results in changes in chromatin structure. Here we present studies of Saccharomyces cerevisiae Spt6, a conserved protein implicated in both transcription elongation and chromatin structure. Our results show that, surprisingly, an spt6 mutant permits aberrant transcription initiation from within coding regions. Furthermore, transcribed chromatin in the spt6 mutant is hypersensitive to micrococcal nuclease, and this hypersensitivity is suppressed by mutational inactivation of RNA polymerase II. These results suggest that Spt6 plays a critical role in maintaining normal chromatin structure during transcription elongation, thereby repressing transcription initiation from cryptic promoters. Other elongation and chromatin factors, including Spt16 and histone H3, appear to contribute to this control.

http://science.sciencemag.org/content/sci/301/5636/1096.full.pdf

Transcription Elongation Factors Repress Transcription Initiation from Cryptic Sites

Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis

Post-transcriptional Control of Cyclooxygenase-2 Gene Expression THE ROLE OF THE 3′-UNTRANSLATED REGION

Iron is an essential element for all eukaryotes. The facile ability of iron to gain and lose electrons permits its participation in a wide variety of oxidation-reduction reactions. Further, the ability of iron as a component of heme to bind oxygen makes it indispensable as an oxygen carrier and sensor, particularly in vertebrates where the size of the organism provides a barrier to simple oxygen diffusion requiring specialized oxygen transport. Iron is found as a prosthetic group on proteins in various forms: elemental iron, oxoiron or oxoiron-zinc, heme, and iron-sulfur clusters. While the diversity of iron-containing proteins and the reactions they participate in highlights the usefulness of iron in biochemical reactions, iron is problematic for two reasons. First, the same facile property of electron gain and loss that permits iron to participate in oxidation-reduction reactions permits iron to donate electrons to oxygen or hydrogen peroxide, generating toxic oxygen radicals, superoxide anion and hydroxyl radical. The existence of these oxygen radicals has led to the evolution of enzyme systems capable of either preventing or removing oxygen radicals once formed. Loss of these enzymes, such as superoxide dismutase, leads to increased cellular damage and compromised growth. Because iron can be toxic, all iron acquisition systems are highly regulated in order to restrict the concentration of iron within biological fluids, extending from the cytosol of yeast to the plasma of vertebrates. Furthermore, regulation of iron acquisition is one of the most critical steps in maintaining iron homeostasis because eukaryotes do not have regulated mechanisms of iron egress. The second reason that iron is problematic is that bioavailable iron is scarce. Iron is the fourth most abundant element on earth but is not uniformly distributed. Iron is scarce both because there are vast geographical areas, such as the oceans, which are iron-poor and because iron, when abundant, is found in a biologically inaccessible form. Iron’s proclivity to react with oxygen has resulted in the predominant form of iron being the insoluble ferric hydroxide. Great investment of cellular resources is required to make iron bioavailable. Even with such effort, the external concentration of iron is often limiting, leading to cellular responses that “triage” iron to biochemical pathways that most require it. We have come to understand that not only is the acquisition and storage of iron highly regulated, but the processes that divert iron among intracellular biochemical pathways are also * Corresponding author. † Texas A&M University. ‡ University of Utah. Craig D. Kaplan obtained a B.S. in Biology and Latin Language and Literature from the University of Michigan, Ann Arbor, Michigan, in 1995, and a Ph.D. in Genetics from Harvard University in 2003 under the supervision of Dr. Fred Winston at Harvard Medical School. His Ph.D. dissertation focused on the regulation of chromatin structure and transcription by the RNA Polymerase II elongation factor Spt6. Much of this manuscript was written while he was a postdoctoral fellow with Dr. Roger Kornberg at the Stanford University School of Medicine, investigating the mechanisms of RNA Polymerase II elongation control, both innate and factor-mediated. He has recently joined the faculty in the Department of Biochemistry and Biophysics, at Texas A&M University, as an assistant professor. Chem. Rev. 2009, 109, 4536–4552 4536

Craig D. Kaplan

Papers

Transcription Elongation Factors Repress Transcription Initiation from Cryptic Sites

Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis

Post-transcriptional Control of Cyclooxygenase-2 Gene Expression THE ROLE OF THE 3′-UNTRANSLATED REGION

Iron acquisition and transcriptional regulation.

The RNA Polymerase II Trigger Loop Functions in Substrate Selection and Is Directly Targeted by α-Amanitin