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Chromatin‐bound proteins underlie several fundamental cellular functions, such as control of gene expression and the faithful transmission of genetic and epigenetic information. Components of the chromatin proteome (the “chromatome”) are essential in human life, and mutations in chromatin‐bound proteins are frequently drivers of human diseases, such as cancer. Proteomic characterization of chromatin...
Methyl CpG binding protein 2 (MeCP2) was initially isolated as an exclusive reader of DNA methylated at CpG. This recognition site, was subsequently extended to other DNA methylated residues and it has been the persisting dogma that binding to methylated DNA constitutes its physiologically relevant role. As we review here, two very recent papers fundamentally change our understanding of the interactions...
During brain development, neural precursor cells (NPCs) in different brain regions produce different types of neurons, and each of these regions plays a different role in the adult brain. Therefore, precise regionalization is essential in the early stages of brain development, and irregular regionalization has been proposed as the cause of neurodevelopmental disorders. The mechanisms underlying brain...
The DNA‐passage activity of topoisomerase II accidentally produces DNA knots and interlinks within and between chromatin fibers. Fortunately, these unwanted DNA entanglements are actively removed by some mechanism. Here we present an outline on DNA knot formation and discuss recent studies that have investigated how intracellular DNA knots are removed. First, although topoisomerase II is able to minimize...
Heritable traits are predominantly encoded within genomic DNA, but it is now appreciated that epigenetic information is also inherited through DNA methylation, histone modifications, and small RNAs. Several examples of transgenerational epigenetic inheritance of traits have been documented in plants and animals. These include even the inheritance of traits acquired through the soma during the life...
The lysine demethylase KDM5A collaborates with PARP1 and the histone variant macroH2A1.2 to modulate chromatin to promote DNA repair. Indeed, KDM5A engages poly(ADP‐ribose) (PAR) chains at damage sites through a previously uncharacterized coiled‐coil domain, a novel binding mode for PAR interactions. While KDM5A is a well‐known transcriptional regulator, its function in DNA repair is only now emerging...
Eukaryotic genome DNA is wrapped around core histones and forms a nucleosome structure. Together with associated proteins and RNAs, these nucleosomes are organized three‐dimensionally in the cell as chromatin. Emerging evidence demonstrates that chromatin consists of rather irregular and variable nucleosome arrangements without the regular fiber structure and that its dynamic behavior plays a critical...
Phenotypic plasticity is a crucial feature of aggressive cancer, providing the means for cancer progression. Stochastic changes in tumor cell transcriptional programs increase the chances of survival under any condition. I hypothesize that unstable chromatin permits stochastic transitions between transcriptional programs in aggressive cancers and supports non‐genetic heterogeneity of tumor cells as...
The spatial organization of genomes is becoming increasingly understood. In mammals, where it is most investigated, this organization ties in with transcription, so an important research objective is to understand whether gene activity is a cause or a consequence of genome folding in space. In this regard, the phenomena of X‐chromosome inactivation and reactivation open a unique window of investigation...
Error‐free genome duplication and accurate cell division are critical for cell survival. In all three domains of life, bacteria, archaea, and eukaryotes, initiator proteins bind replication origins in an ATP‐dependent manner, play critical roles in replisome assembly, and coordinate cell‐cycle regulation. We discuss how the eukaryotic initiator, Origin recognition complex (ORC), coordinates different...