The interaction landscape between transcription factors and the nucleosome

Zhu, Fei; Farnung, Lucas; Kaasinen, Eevi; Sahu, Biswajyoti; Yin, Yimeng; Wei, Bei; Dodonova, S.O.; Nitta, Kazuhiro R.; Morgunova, Ekaterina; Taipale, Minna; Cramer, Patrick; Taipale, Jussi

doi:10.1038/s41586-018-0549-5

Cited by 304 publications

(295 citation statements)

References 59 publications

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“…1e). This is in line with published data for the highly homologous ETS domain of SPIB, which showed a clear binding preference for linker and nucleosome entry sites in the NCAP-SELEX assay 19 . These in vitro binding studies suggested that PU.1 alone is indeed restricted by both DNA methylation and chromatin.…”

Section: Pu1 Binding Across Multiple Cell Types In Vivo and In Vitrosupporting

confidence: 92%

Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1

et al. 2020

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Establishing gene regulatory networks during differentiation or reprogramming requires master or pioneer transcription factors (TFs) such as PU.1, a prototype master TF of hematopoietic lineage differentiation. To systematically determine molecular features that control its activity, here we analyze DNA-binding in vitro and genome-wide in vivo across different cell types with native or ectopic PU.1 expression. Although PU.1, in contrast to classical pioneer factors, is unable to access nucleosomal target sites in vitro, ectopic induction of PU.1 leads to the extensive remodeling of chromatin and redistribution of partner TFs. De novo chromatin access, stable binding, and redistribution of partner TFs both require PU.1's N-terminal acidic activation domain and its ability to recruit SWI/SNF remodeling complexes, suggesting that the latter may collect and distribute co-associated TFs in conjunction with the non-classical pioneer TF PU.1.

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Section: Pu1 Binding Across Multiple Cell Types In Vivo and In Vitrosupporting

confidence: 92%

Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1

et al. 2020

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“…A very interesting finding from our work is that the PWWP reader domain can bind across both DNA gyres of the nucleosome. Such cross-gyre binding of nucleosome-interacting proteins was proposed already 25 years ago 44 , but only observed very recently, when a study revealed that transcription factors of the T-box family use such cross-gyre binding 45 . Recent structures of chromatin remodeling enzymes and a retroviral intasome bound to nucleosomes also showed cross-gyre binding through multiple domains [46][47][48][49][50] , but with different geometries and at distinct SHL positions.…”

Section: Discussionmentioning

confidence: 97%

Structure of H3K36-methylated nucleosome–PWWP complex reveals multivalent cross-gyre binding

Wang

Farnung

Dienemann

et al. 2019

Nat Struct Mol Biol

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C ovalent modifications of nucleosomes regulate chromatinbased processes such as DNA transcription, replication and repair. Many modifications occur on the accessible histone tails that protrude from the nucleosome core particle. These modifications include acetylation and methylation of lysine residues and are recognized by 'reader' domains that recruit various proteins. The molecular basis for how reader domains recognize histone modifications has been provided by structural studies of reader domain-histone peptide complexes 1 .Some reader domains not only bind modified histone tails, but can additionally bind to DNA. Of over 20 types of reader domains, at least four (PWWP, Tudor, chromo and bromo) are known to bind both the modified histone and DNA 2,3 . These reader domains are predicted to recognize the histone modification in the context of nucleosomal DNA, with both types of interactions contributing to the affinity of the domain for modified nucleosomes. However, such multivalent binding of a reader domain was thus far not observed directly.A widespread type of reader domain that can engage in multivalent interactions is the PWWP (Pro-Trp-Trp-Pro motif) domain. This domain was identified in the protein product of the Wolf-Hirschhorn syndrome candidate gene 1 (WHSC1) and in proteins related to hepatoma-derived growth factor (HDGF) 4,5 . It was later found in the DNA methyltransferase DNMT3B and the DNA repair protein MSH6 (refs. 6,7 ). The PWWP domain is a reader of methylated histone tails and comprises a five-stranded N-terminal β-barrel and two C-terminal α-helices 8 . The β-barrel harbors a conserved aromatic cage that binds a methyl-lysine residue 9 , as also observed for other reader domains of the 'Royal' superfamily such as Tudor, chromo, Agenet and MBT domains 10 .Most PWWP domains bind the histone H3 N-terminal tail that is di-or tri-methylated at lysine 36 (H3K36me2 or H3K36me3) [11][12][13][14][15][16] . The H3K36me3 modification occurs in gene bodies of transcribed chromatin in eukaryotic species from yeast to human 17 . This modification is mainly generated by SETD2 (KMT3A), a lysine methyltransferase associated with elongating RNA polymerase II (Pol II) 18,19 . H3K36me3 has functions in transcription elongation, alternative splicing, DNA methylation, DNA damage signaling, and repression of cryptic transcription and histone exchange 20 .The PWWP domain binds methylated H3K36 histone tail peptides with much lower affinity 11,15 than other methyl-lysine reader domains such as PHD fingers 21 . To achieve high-affinity binding, PWWP domains rely on additional interactions with DNA. Indeed, the PWWP domain was first described as a DNA-binding fold 7,22 , and the PWWP domain in Pdp1 was found to bind both a methylated histone peptide and DNA 23 . Nucleosomal DNA was shown to contribute strongly to high-affinity binding of a PWWP domain to an H3K36-methylated nucleosome 24,25 , and it was predicted that the domain may bind both DNA gyres 25 . Very recently, structures were reported of the PWWP domai...

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“…On the other hand, nucleosome displacement actively enforced by chromatin remodelers enables the selective exposure of the fraction of the regulatory information available for transcriptional control in a given cell type (Barozzi et al 2014). Such a process is instructed by sequence-specific DNA-binding proteins able to recognize motifs in nucleosomal DNA (Zhu et al 2018) and instigate nucleosome displacement or remodeling (Zaret and Carroll 2011). While their mode of binding to nucleosomal DNA can be extremely diversified (Zhu et al 2018), such TFs have been collectively termed "pioneers" and coincide at least in part with lineage-determining TFs, whose expression is triggered by microenvironmental cues in the developmental niche of individual tissues.…”

mentioning

confidence: 99%

“…Such a process is instructed by sequence-specific DNA-binding proteins able to recognize motifs in nucleosomal DNA (Zhu et al 2018) and instigate nucleosome displacement or remodeling (Zaret and Carroll 2011). While their mode of binding to nucleosomal DNA can be extremely diversified (Zhu et al 2018), such TFs have been collectively termed "pioneers" and coincide at least in part with lineage-determining TFs, whose expression is triggered by microenvironmental cues in the developmental niche of individual tissues. This is typified by M-CSF (macrophage colony-stimulating factor) induction of the myeloid lineage-determining TF PU.1 in the bone marrow (Mossadegh-Keller et al 2013).…”

mentioning

confidence: 99%

Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

et al. 2019

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Accessibility of the genomic regulatory information is largely controlled by the nucleosome-organizing activity of transcription factors (TFs). While stimulus-induced TFs bind to genomic regions that are maintained accessible by lineage-determining TFs, they also increase accessibility of thousands of cis-regulatory elements. Nucleosome remodeling events underlying such changes and their interplay with basal positioning are unknown. Here, we devised a novel quantitative framework discriminating different types of nucleosome remodeling events in micrococcal nuclease ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) data sets and used it to analyze nucleosome dynamics at stimulus-regulated cis-regulatory elements. At enhancers, remodeling preferentially affected poorly positioned nucleosomes while sparing well-positioned nucleosomes flanking the enhancer core, indicating that inducible TFs do not suffice to overrule basal nucleosomal organization maintained by lineage-determining TFs. Remodeling events appeared to be combinatorially driven by multiple TFs, with distinct TFs showing, however, different remodeling efficiencies. Overall, these data provide a systematic view of the impact of stimulation on nucleosome organization and genome accessibility in mammalian cells.

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The interaction landscape between transcription factors and the nucleosome

Cited by 304 publications

References 59 publications

Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1

Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1

Structure of H3K36-methylated nucleosome–PWWP complex reveals multivalent cross-gyre binding

Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

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