New insights into unwrapping DNA from the nucleosome from a single-molecule optical tweezers method.
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Chromatin↗
Biomedical subjects
Jeffrey C Hansen
Publications and source records attributed to Jeffrey C Hansen.
The SIN domain of the histone octamer is essential for intramolecular folding of nucleosomal arrays.
The SIN domain within histones H3 and H4 is defined by a set of single amino acid substitutions that were initially identified as mutations that alleviate the transcriptional defects associated with inactivation of the SWI/SNF chromatin remodeling complex. Here we use recombinant histones to investigate how Sin- versions of H4 alter the structure of nucleosomal arrays. We find that an R45C substitution within the SIN domain of H4 does not disrupt nucleosome positioning nor does this Sin- version alter the accessibility of nucleosomal DNA. In contrast, we find that the R45C substitution eliminates Mg2+-dependent, intramolecular folding of the nucleosomal arrays. Our results suggest that Sin- versions of histones may alleviate the need for SWI/SNF in vivo by disrupting higher-order chromatin folding.
Adenosine Triphosphate↗
The essential histone variant H2A.Z regulates the equilibrium between different chromatin conformational states.
Explaining the determinants involved in regulating the equilibrium between different chromatin structural states is fundamental to understanding differential gene expression. Histone variant H2A.Z is essential to chromatin architecture in higher eukaryotes but its role has not yet been explained. We show here that H2A.Z facilitates the intramolecular folding of nucleosomal arrays while simultaneously inhibiting the formation of highly condensed structures that result from intermolecular association. This makes a case for H2A.Z playing a fundamental role in creating unique chromatin domains poised for transcriptional activation. These results provide new insights into understanding how chromatin fiber dynamics can be altered by core histone variants to potentially regulate genomic function.
Animals↗
Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes.
Members of the ATP-dependent family of chromatin remodeling enzymes play key roles in the regulation of transcription, development, DNA repair and cell cycle control. We find that the remodeling activities of the ySWI/SNF, hSWI/SNF, xMi-2 and xACF complexes are nearly abolished by incorporation of linker histones into nucleosomal array substrates. Much of this inhibition is independent of linker histone-induced folding of the arrays. We also find that phosphorylation of the linker histone by Cdc2/Cyclin B kinase can rescue remodeling by ySWI/SNF. These results suggest that linker histones exert a global, genome-wide control over remodeling activities, implicating a new, obligatory coupling between linker histone kinases and ATP-dependent remodeling enzymes.
APOBEC-1 Deaminase↗
Conformational dynamics of the chromatin fiber in solution: determinants, mechanisms, and functions.
Chromatin fibers are dynamic macromolecular assemblages that are intimately involved in nuclear function. This review focuses on recent advances centered on the molecular mechanisms and determinants of chromatin fiber dynamics in solution. Major points of emphasis are the functions of the core histone tail domains, linker histones, and a new class of proteins that assemble supramolecular chromatin structures. The discussion of important structural issues is set against a background of possible functional significance.
Animals↗