Nucleosome structure(s) and stability: Variations on a theme
ABSTRACT Chromatin is a highly regulated, modular nucleoprotein complex that is central to many processes in eukaryotes. The organization of DNA into nucleosomes and higher-order structures has profound implications for DNA accessibility. Alternative structural states of the nucleosome, and the thermodynamic parameters governing its assembly and disassembly, need to be considered in order to understand how access to nucleosomal DNA is regulated. In this review, we provide a brief historical account of how the overriding perception regarding aspects of nucleosome structure has changed over the past thirty years. We discuss recent technical advances regarding nucleosome structure and its physical characterization and review the evidence for alternative nucleosome conformations and their implications for nucleosome and chromatin dynamics.
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- "One mechanism includes changing the chemical composition of DNA by the addition of a methyl group that is usually associated with transcriptional repression (Fig. 1) (Smith and Meissner 2013). DNA is wrapped around eight histone proteins to form nucleosomes (Fig. 2A), and a second mechanism involves modifying specific amino acid residues on the histone tails (Fig. 2B) (Andrews and Luger 2011). These posttranslational histone modifications are able to recruit additional proteins that either positively or negatively affect transcription (Fig. 2C) (Barski et al. 2007; Wang et al. 2008). "
ABSTRACT: In a cell, the chromatin state is controlled by the highly regulated interplay of epigenetic mechanisms ranging from DNA methylation and incorporation of different histone variants to posttranslational modification of histones and ATP-dependent chromatin remodeling. These changes alter the structure of the chromatin to either facilitate or restrict the access of transcription machinery to DNA. These epigenetic modifications function to exquisitely orchestrate the expression of different genes, and together constitute the epigenome of a cell. In the skin, different epigenetic regulators form a regulatory network that operates to guarantee skin stem cell maintenance while controlling differentiation to multiple skin structures. In this review, we will discuss recent findings on epigenetic mechanisms of skin control and their relationship to skin pathologies.Cold Spring Harbor Perspectives in Medicine 02/2014; 4(2). DOI:10.1101/cshperspect.a015263 · 7.56 Impact Factor
- "If there are real differences in the DNA binding affinities or binding site sizes for the H1.1, H1.4 and H1 0 proteins, the differences must be attributed to the different sequences and/or charge and charge distribution in the C-terminal domains of these proteins. It is generally accepted that H1, or linker histone, binds to DNA as it enters and/or exits the nucleosome    . Two different models for H1 binding place the H1 protein across the nucleosome with H1 interacting with two or three patches of the nucleosomal DNA on the same side of the nucleosome  or alternatively locate the H1 so that it binds to a continuous and more linear linker DNA region . "
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- "Eukaryotic genome is organized into distinct chromosomes that are formed by a nucleoprotein complex called chromatin. Chromatin consists of the nucleosomes, in which 147 base-pairs of genomic DNA form a loop around the histone octamer core represented by two molecules of each core histone (H2A, H2B, H3 and H4) (Andrews and Luger, 2011). Nucleosomes are connected by non-histone associated linker DNA of approximately 10-80 bp length resulting in a formation of the " beads on the string " structures, which are folded into 30 nm fiber (Felsenfeld and Groudine, 2003). "
ABSTRACT: The nucleus is a complex and highly compartmentalized organelle, which undergoes major organization changes during cell differentiation, allowing cells to become specialized and fulfill their functions. During terminal differentiation of the epidermal keratinocytes, the nucleus undergoes a programmed transformation from active status, associated with execution of the genetic programs of cornification and epidermal barrier formation, to a fully inactive condition and becomes a part of the keratinized cells of the cornified layer. Tremendous progress achieved within the past two decades in understanding the biology of the nucleus and epigenetic mechanisms controlling gene expression allowed defining several levels in the regulation of cell differentiation-associated gene expression programs, including an accessibility of the gene regulatory regions to DNA-protein interactions, covalent DNA and histone modifications, and ATP-dependent chromatin remodeling, as well as higher-order chromatin remodeling and nuclear compartmentalization of the genes and transcription machinery. Here, we integrate our current knowledge of the mechanisms controlling gene expression during terminal keratinocyte differentiation with distinct levels of chromatin organization and remodeling. We also propose directions to further explore the role of epigenetic mechanisms and their interactions with other regulatory systems in the control of keratinocyte differentiation in normal and diseased skin.Journal of Investigative Dermatology 07/2012; 132(11):2505-21. DOI:10.1038/jid.2012.182 · 6.37 Impact Factor