Predicting nucleosome positioning using a duration Hidden Markov Model

Li, Xi; Fondufe‐Mittendorf, Yvonne; Xia, Lei; Flatow, Jared; Widom, Jonathan; Wang, Ji-Ping Z

doi:10.1186/1471-2105-11-346

Cited by 132 publications

(170 citation statements)

References 21 publications

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“…4). These results were also in agreement with the Nucleosome Positioning Prediction Engine (NuPoP) (51). As predicted by NuPoP, PolyA_1, PolyA_3, and PolyA_4 all had changes in nucleosome positioning compared with the wild-type sequence.…”

Section: Discussionsupporting

confidence: 85%

Single-cell nucleosome mapping reveals the molecular basis of gene expression heterogeneity

Small

Wang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Nucleosomes limit access to DNA, which antagonizes gene expression and prevents recruitment of transcription factors that cannot bind DNA wrapped around the histone octamer. Numerous studies using large cell populations determined that active genes promoters tend to be nucleosome-depleted. We developed a method to examine nucleosome positioning in single cells and revealed significant heterogeneity of nucleosome configurations within a population. In an inactive gene loaded with nucleosomes, a small subpopulation of nucleosome-depleted cells exists that were engaged in transcription. Single-cell mapping revealed that even in apparently nucleosome-free regions, some cells were occupied by nucleosomes. These data reveal an underlying complexity of nucleosome positioning and its role in regulating gene expression.

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Section: Discussionsupporting

confidence: 85%

Single-cell nucleosome mapping reveals the molecular basis of gene expression heterogeneity

Small

Wang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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103

123

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“…3D). Therefore, the phasing pattern of nucleosome occupancy can be roughly predicted using a nucleosome-linker DNA model based on a duration hidden Markov model (dHMM) (45) (Fig. 3D).…”

Section: Significancementioning

confidence: 99%

Chemical map of Schizosaccharomyces pombe reveals species-specific features in nucleosome positioning

Moyle-Heyrman¹,

Zaichuk²,

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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115

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Using a recently developed chemical approach, we have generated a genome-wide map of nucleosomes in vivo in Schizosaccharomyces pombe (S. pombe) at base pair resolution. The shorter linker length previously identified in S. pombe is due to a preponderance of nucleosomes separated by ∼4/5 bp, placing nucleosomes on opposite faces of the DNA. The periodic dinucleotide feature thought to position nucleosomes is equally strong in exons as in introns, demonstrating that nucleosome positioning information can be superimposed on coding information. Unlike the case in Saccharomyces cerevisiae, A/T-rich sequences are enriched in S. pombe nucleosomes, particularly at ±20 bp around the dyad. This difference in nucleosome binding preference gives rise to a major distinction downstream of the transcription start site, where nucleosome phasing is highly predictable by A/T frequency in S. pombe but not in S. cerevisiae, suggesting that the genomes and DNA binding preferences of nucleosomes have coevolved in different species. The poly (dA-dT) tracts affect but do not deplete nucleosomes in S. pombe, and they prefer special rotational positions within the nucleosome, with longer tracts enriched in the 10-to 30-bp region from the dyad. S. pombe does not have a welldefined nucleosome-depleted region immediately upstream of most transcription start sites; instead, the −1 nucleosome is positioned with the expected spacing relative to the +1 nucleosome, and its occupancy is negatively correlated with gene expression. Although there is generally very good agreement between nucleosome maps generated by chemical cleavage and micrococcal nuclease digestion, the chemical map shows consistently higher nucleosome occupancy on DNA with high A/T content.chromatin structure | heterochromatin | gene regulation E ukaryotic DNA is organized into nucleosome arrays that facilitate proper genome compaction and regulation of the genetic information. Genome-wide nucleosome maps from different organisms have provided important insights into how nucleosome positioning regulates chromosome functions (1-6). It is commonly accepted that the DNA sequence itself plays a major role in the exact positions where histone octamers bind DNA to form nucleosomes (7-9). Most remarkably, nucleosomes prefer special dinucleotide motifs at specific rotational angles within the nucleosome core (10, 11) and disfavor poly (dA-dT) tracts (12-15). Although the ability of DNA to interact with the histone core is important, nucleosome occupancy is influenced by additional extrinsic factors, including species-specific DNA binding proteins (16), ATP-dependent remodeling complexes (17,18), and the transcription machinery (19)(20)(21)(22).The underlying mechanisms for the species-or cell typespecific nucleosome positioning features have not been well understood. The fission yeast Schizosaccharomyces pombe and the budding yeast Saccharomyces cerevisiae are two highly diverged model organisms widely used to study basic biological processes in eukaryotes (23). Although similar in siz...

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“…To test this idea, we analyzed these regions with two in silico nucleosome prediction algorithms that predict nucleosome occupancy based on DNA sequence characteristics (61,62) We found that some sites that depend on Mit1 for prevention of nucleosome-free regions appear to be particularly refractory to octamer occupancy and lie near positions predicted to have relatively well-positioned nucleosomes, particularly at REII in the mating-type region and telomere 2R (Fig. 5A and B).…”

Section: ⌬Phd and Mit1mentioning

confidence: 99%

“…The predicted low affinity of these sequences is likely due to low G/C content and a high percentage of DNA with 5-mers of exclusively A/T nucleotides ( Fig. 5C and D), both of which disfavor nucleosome formation (62,63). This would suggest that Mit1 may play a critical role in moving nucleosomes onto DNA sequences that are energetically unfavorable for nucleosome positioning.…”

Section: ⌬Phd and Mit1mentioning

confidence: 99%

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes within Heterochromatin To Suppress Transcription

Creamer

Job

Shanker

et al. 2014

Molecular and Cellular Biology

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Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/histone deacetylase (HDAC) repressor complex (SHREC) and is known to repress transcription at regions of heterochromatin. However, how Mit1 modifies chromatin to silence transcription is largely unknown. Here we report that Mit1 mobilizes histone octamers in vitro and requires ATP hydrolysis and conserved chromatin tethering domains, including a previously unrecognized chromodomain, to remodel nucleosomes and silence transcription. Loss of Mit1 remodeling activity results in nucleosome depletion at specific DNA sequences that display low intrinsic affinity for the histone octamer, but its contribution to antagonizing RNA polymerase II (Pol II) access and transcription is not restricted to these sites. Genetic epistasis analyses demonstrate that SHREC subunits and the transcriptioncoupled Set2 histone methyltransferase, which is involved in suppression of cryptic transcription at actively transcribed regions, cooperate to silence heterochromatic transcripts. In addition, we have demonstrated that Mit1's remodeling activity contributes to SHREC function independently of Clr3's histone deacetylase activity on histone H3 K14. We propose that Mit1 is a chromatin remodeling factor that cooperates with the Clr3 histone deacetylase of SHREC and other chromatin modifiers to stabilize heterochromatin structure and to prevent access to the transcriptional machinery.

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Predicting nucleosome positioning using a duration Hidden Markov Model

Cited by 132 publications

References 21 publications

Single-cell nucleosome mapping reveals the molecular basis of gene expression heterogeneity

Single-cell nucleosome mapping reveals the molecular basis of gene expression heterogeneity

Chemical map of Schizosaccharomyces pombe reveals species-specific features in nucleosome positioning

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes within Heterochromatin To Suppress Transcription

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