These mutations cause a reduction in the overall levels of methylation on H3K27 by targeting the active site of SET-domain containing methyl transferases [45••]. The loss of H3K27 methylation is predicted

to disrupt a feedback loop that regulates the polycomb repressor complex 2 (PCR2), which then promotes the cancer state. Thus, histones can play a pivotal role find more in the progression of the disease state, making them potential candidates to consider for therapeutic targeting. As is evident from the large body of literature on histones and their variants, nucleosomes and their structure, and chromatin organization in vitro and in vivo, this topic is a continuously evolving chapter in the study of genomes. Despite almost 40 years of steady progress on understanding chromatin, profound open questions persist that make this field one of the most exciting to investigate. Do histone variants have different preferences for particular DNA sequences?

Do histones re-associate with the same DNA sequence after being disrupted? Is there true molecular memory at sites that are to be marked for the next cell cycle? How is such memory over-ridden when cells embark on different developmental programs? How does the vigorous compression in the mitotic chromosome physically affect the position and stability of various types of nucleosomes? When cells age or transit into resting phase, how does the proportion of histone variants and nucleosome positions change, and how do such phenomena affect the rate of gene expression, DNA repair, Lck I-BET-762 solubility dmso remodeling and replication? All these questions await answers, which will eventually bring a more complete conceptual framework of the behaviors

used to regulate genetic accessibility by these tiny, but crucial proteins, the tricksters of the genome. Papers of particular interest, published within the period of review, have been highlighted as: • of special interest “
“Current Opinion in Genetics & Development 2014, 25:15–21 This review comes from a themed issue on Genome architecture and expression Edited by Victor Corces and David L Levens For a complete overview see the Issue and the Editorial Available online 22nd December 2013 0959-437X/$ – see front matter, © 2013 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.gde.2013.10.013 DNA is a dynamic molecule. In its relaxed state it adopts a right-handed helically coiled conformation, the detailed structure of which is dependent on the localised sequence. Winding DNA around its axis introduces supercoils increasing the free energy stored in the molecule; winding in the same direction as the helix introduces positive supercoiling whereas winding in the opposite direction generates negative supercoiling [1 and 2]. In addition to supercoiling derived from changes in DNA twist, it is also a product of the coiling or bending of the helix in space, a parameter commonly termed writhe.