Crystal structure of globular domain of histone H5 and its implications for nucleosome binding

Ramakrishnan, V.; Finch, J.T.; Graziano, Vito; Lee, P L; Sweet, Robert M.

doi:10.1038/362219a0

Cited by 746 publications

(614 citation statements)

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“…However, the fact that the globular domain of H1 alone provided the majority of the observed repression (Fig. 1) indicates that repression is largely mediated by the binding of the globular "winged helix" structure (41). Indeed, the observation that H1 binding to reconstituted nucleosome cores is dependent on the presence of linker DNA (i.e.…”

Section: Discussionmentioning

confidence: 92%

H1-mediated Repression of Transcription Factor Binding to a Stably Positioned Nucleosome

Juan

Utley

Vignali

et al. 1997

Journal of Biological Chemistry

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Biochemical studies have implicated both nucleosome core assembly and/or the subsequent binding of the linker histone H1 in transcriptional repression (4 -9). Because the affinities of sequence-specific DNA-binding proteins for nucleosomal DNA are often dramatically reduced compared with free DNA (reviewed in Ref. 10), nucleosomes repress the transcriptional process, at least in part, by inhibiting access of activator proteins to their cognate binding sites in chromatin. Factor occupancy of binding sites in nucleosomal arrays is most likely achieved through multiple mechanisms involving nucleosome disruption, nucleosome displacement in trans, or histone octamer sliding in cis (reviewed in Ref. 11). The idea of mobile nucleosomes (i.e. nucleosome sliding) is attractive in that it has the potential to create transient accessibility of factors to their binding sites. Its potential importance is further implicated in studies that illustrate the differential affinity of factors for sites at different translational and rotational positions within nucleosomes (12-15). Using a model system consisting of chromatin assembled on tandemly repeated sea urchin 5 S rRNA nucleosome positioning sequences (16), Bradbury and colleagues (17, 18) have previously reported that nucleosomes adopt a dominant position surrounded by minor positions 10 base pairs apart (i.e. in the same rotational frame). These data indicate that the cluster of octamer positions is in dynamic equilibrium in low ionic strength conditions. In the presence of the linker histone H1, this mobility is inhibited (19). The same group found that this short range sliding behavior also applies to bulk mononucleosomes and nucleosomes reconstituted onto sequences of the Alu family of ubiquitous repeats. Thus, they proposed that nucleosome mobility is a general behavior (20). Moreover, H1-mediated reduction in nucleosome mobility has been implicated in repression of transcription of a dinucleosome reconstituted onto a dimerized Xenopus somatic 5 S rRNA gene (2).In our previous studies, we reported for the first time direct inhibition of factor binding by the association of H1 with nucleosome cores. The binding of H1 to form a chromatosome significantly repressed the subsequent binding of USF 1 but only slightly inhibited GAL4-AH binding (1). In this report, we extend these studies to explore the underlying mechanisms by which H1 repressed USF binding. The results illustrate H1-mediated repression of USF binding to a stably positioned nucleosome. Thus, H1 repression in this instance occurred in the absence of nucleosome mobility. In addition, H1 repressed USF binding to a site on the opposite side of the histone octamer from the entry and exit points of the linker DNA. These data are consistent with a mechanism by which H1 stabilizes histone octamer-DNA interactions, thus reducing transient exposure of factor binding sites. MATERIALS AND METHODSPreparation of DNA Probes-The 183-bp probe DNAs, referred to as GU or UG probes, were either directly generated by BamHI digesti...

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Section: Discussionmentioning

confidence: 92%

H1-mediated Repression of Transcription Factor Binding to a Stably Positioned Nucleosome

Juan

Utley

Vignali

et al. 1997

Journal of Biological Chemistry

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“…Analysis with the software DALI 40 showed that only the N-terminal portion of the structure -that is, the helix core and the β-hairpin arm -bears minor similarity to the globular domain of histone H5 (Z-score 5.3) 41 . The structure of the globular domain of histone H5 belongs to the superfamily of winged-helix DNA binding proteins.…”

Section: Overall Fold Of the Dep Domain Of Mdvl1mentioning

confidence: 99%

Untitled

et al. 2000

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The DEP domain of Dishevelled (Dvl) proteins transduces signals to effector proteins downstream of Dvl in the Wnt pathway. Here we report that DEP-containing mutants inhibit Wnt-induced, but not Dvl-induced, activation of the transcription factor Lef-1. This inhibitory effect is weakened by a K434M mutation. Nuclear magnetic resonance spectroscopy revealed that the DEP domain of mouse Dvl1 comprises a three-helix bundle, a β-hairpin 'arm' and two short β-strands at the Cterminal region. Lys 434 is located at the tip of the β-hairpin 'arm'. Based on our findings, we conclude that DEP interacts with regulators upstream of Dvl via a strong electric dipole on the molecule's surface created by Lys 434, Asp 445 and Asp 448; the electric dipole and the putative membrane binding site are at two different locations.The Wnt signaling pathway is a key regulatory pathway for cellular development and growth. Wnt signaling has been extensively studied in Drosophila, Caenorhabditis elegans, Xenopus, and mammalian systems [1][2][3][4][5] . Through genetic studies, a working model of the Wnt signaling pathway has been established. Secreted Wnt proteins bind to Frizzled transmembrane receptors. The receptor-ligand complex activates the Dishevelled (Dsh and Dvl) proteins, which suppress the activity of glycogen synthase kinase-3β (GSK-3β). If its activity is not suppressed, GSK-3β binds to adenomatous polyposis coli (APC) protein and axin and then phosphorylates specific Ser and Thr residues at the N-terminus of β-catenin. In turn, the ubiquitin-proteasome pathway rapidly degrades hyperphosphorylated β-catenin. Wnt activation prevents this process by promoting the cytosolic accumulation and subsequent translocation of β-catenin into the nucleus. Once in the nucleus, β-catenin binds to the transcription factors T-cell factor (Tcf) or lymphoid enhancer factor (Lef) and acts as a transcriptional coactivator 5 . The result is increased expression of Tcf or Lef regulated target genes, such as Myc 6 and the gene encoding cyclin D 7 .© 2000 Nature America Inc. Correspondence should be addressed to: J.Z. Jie.Zheng@stjude.org. HHS Public Access DEP domain interacts with upstream regulators of DvlWe and others have demonstrated that Wnt-1 or Dvl1, when expressed in NIH3T3 cells, can activate the transcription regulator 16,28,29). This activation depends on β-catenin and is suppressed by GSK-3β and axin. To characterize the role of the mDvl1 DEP domain in Wnt signaling, we examined the effect of the Dvl1 N-terminal truncation mutant, DvlC1, on Wnt-induced activation of the transcription factor Lef-1. In Lef dependent reporter gene assays, DvlC1 inhibited Wnt-1 induced Lef-1 activation but not Dvl1 induced Lef-1 activation (Fig. 2). To further characterize the specific sequences that inhibit the Wnt-induced activation, we generated two additional mutants of mDvl1: DvlDEP, which contains only the DEP domain; and DvlC2, which encompasses the sequence downstream of the DEP domain. When expressed in NIH3T3 cells, DvlDEP, like DvlC1, bloc...

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“…Chromatin opening by FoxA in vitro does not require ATP or ATP-dependent chromatin remodelers (Cirillo et al 2002). Notably, the DNA-binding domain of FoxA resembles that of linker histone and binds to one side of a DNA helix along the long axis of DNA, which leaves the other side of DNA to bind core histones (Clark et al 1993;Ramakrishnan et al 1993;Cirillo et al 1998). Thus, the FoxA pioneer factor is structurally suited to recognize its DNA target sites on a nucleosome.…”

Section: The Basis For Pioneer Activity: Nucleosome Binding and Chrommentioning

confidence: 99%

Pioneer transcription factors in cell reprogramming

2014

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A subset of eukaryotic transcription factors possesses the remarkable ability to reprogram one type of cell into another. The transcription factors that reprogram cell fate are invariably those that are crucial for the initial cell programming in embryonic development. To elicit cell programming or reprogramming, transcription factors must be able to engage genes that are developmentally silenced and inappropriate for expression in the original cell. Developmentally silenced genes are typically embedded in ''closed'' chromatin that is covered by nucleosomes and not hypersensitive to nuclease probes such as DNase I. Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as ''pioneer factors'' to initiate events in closed chromatin. Other reprogramming factors appear dependent on pioneer factors for engaging nucleosomes and closed chromatin. However, certain genomic domains in which nucleosomes are occluded by higher-order chromatin structures, such as in heterochromatin, are resistant to pioneer factor binding. Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance our ability to reprogram cell fates at will and is the topic of this review.Cell fate control represents the most extreme form of gene regulation. Genes specific to the function of a particular type of cell may be antagonistic to the function of another type of cell, so nature has evolved diverse regulatory mechanisms to ensure stable patterns of gene activation and repression. In prokaryotes, self-sustaining regulatory networks of transcription factors bound to DNA can be sufficient to regulate gene activation and repression (Ptashne 2011). In eukaryotes, ;200-base-pair (bp) segments of the genome are wound nearly twice around an octamer of the four core histones to form nucleosomes, providing steric constraints on how transcription factors can bind DNA (Kornberg and Lorch 1999). As described below, pioneer transcription factors have the special property of being able to overcome such constraints, enabling the factors to engage closed chromatin that is not accessible by other types of transcription factors (Fig. 1). However, further higher-order packaging of nucleosomes into heterochromatin can occlude access to DNA altogether, presenting an additional barrier to cell fate conversion (Fig. 1). This review focuses on the most recent studies of pioneer factors in cell programming and reprogramming, how pioneer factors have special chromatinbinding properties, and facilitators and impediments to chromatin binding. We project that such knowledge will greatly aid future efforts to change the fates of cells at will for research, diagnostic, and therapeutic purposes.

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Crystal structure of globular domain of histone H5 and its implications for nucleosome binding

Cited by 746 publications

References 41 publications

H1-mediated Repression of Transcription Factor Binding to a Stably Positioned Nucleosome

H1-mediated Repression of Transcription Factor Binding to a Stably Positioned Nucleosome

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Pioneer transcription factors in cell reprogramming

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