Picking a nucleosome lock: Sequence- and structure-specific recognition of the nucleosome
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Mini-Review Picking a nucleosome lock: Sequence- and structure-specific recognition of the nucleosome MATTHEW M MAKOWSKI1,2, GUILLAUME GAULLIER1,2 KAROLIN LUGER1,2* 1
and
Department of Biochemistry, University of Colorado Boulder, Boulder, CO, USA 2
Howard Hughes Medical Institute, Chevy Chase, MD, USA
*Corresponding author (Email, [email protected])
The nucleosome presents a formidable barrier to DNA-templated transcription by the RNA polymerase II machinery. Overcoming this transcriptional barrier in a locus-specific manner requires sequence-specific recognition of nucleosomal DNA by ‘pioneer’ transcription factors (TFs). Cell fate decisions, in turn, depend on the coordinated action of pioneer TFs at cell lineage-specific gene regulatory elements. Although it is already appreciated that pioneer factors play a critical role in cell differentiation, our understanding of the structural and biochemical mechanisms by which they act is still rapidly expanding. Recent research has revealed novel insight into modes of nucleosome-TF binding and uncovered kinetic principles by which nucleosomal DNA compaction affects both TF binding and residence time. Here, we review progress and argue that these structural and kinetic studies suggest new models of gene regulation by pioneer TFs. Keywords.
Nucleosome; pioneer factors; transcription factors; transcriptional regulation
The same essential genome is replicated faithfully in nearly every one of hundreds of diverse cell types (and in *37 trillion cells) in the human body. Differentiation into heterogeneous cell phenotypes from totipotent progenitors requires differential gene expression of the same underlying genetic information (Levine and Davidson 2005; Lee and Young 2013). During differentiation, genes might be turned ‘on’ during cell differentiation, as with lineage restricted genes, or ‘off’, for example pluripotency genes or genes specific to other lineages. Cell type classification often uses these global differences in gene expression patterns to categorize cell types based on the expression of characteristic lineage marking genes or gene sets (Regev et al. 2017). Many molecular mechanisms regulate differential gene expression. The nucleosome is a tertiary complex composed of 147 base pairs of DNA wrapped
This article is part of the Topical Collection: Chromatin Biology and Epigenetics. http://www.ias.ac.in/jbiosci
around an octameric complex of histone proteins. This DNA configuration effectively compacts and distorts the nucleosomal DNA, occludes much of the histonefacing DNA surface over its entire 147 bp, and presents a serious barrier to effective transcription (Luger et al. 1997; Kujirai et al. 2018; Farnung et al. 2018; Ehara et al. 2019; Zhou et al. 2019). Thus, one key mechanism of gene expression regulation is the compaction of transcriptional and gene regulatory elements by nucleosomes. Gene regulation via nucleosome occlusion of a regulatory or transcriptional element, in t
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