Unsupervised pattern discovery in human chromatin structure through genomic segmentation

Hoffman, Michael M.; Buske, Orion J.; Wang, Jie; Weng, Zhiping; Bilmes, Jeff; Noble, William Stafford

doi:10.1038/nmeth.1937

Cited by 568 publications

(534 citation statements)

References 33 publications

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“…Book-ended bins that have the same state are merged. The output of this process is genome segmentation into variable-width non-overlapping chromatin states similar to Segway (Hoffman et al, 2012) and ChromHMM (Ernst and Kellis, 2012). …”

Section: Methodsmentioning

confidence: 99%

Human Promoters Are Intrinsically Directional

et al. 2015

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Divergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that up to half of promoters are unidirectional and that unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters.

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Section: Methodsmentioning

confidence: 99%

Human Promoters Are Intrinsically Directional

et al. 2015

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“…Combinations of histone modifications are often observed together in chromatin states, patterns indicative of distinct modes of biological activity. These patterns may be identified by integrating multiple histone modification ChIP-seq data sets using the ChromHMM 97 or SegWay 98 algorithms.…”

Section: Analytical Techniques For Bias Correctionmentioning

confidence: 99%

Identifying and mitigating bias in next-generation sequencing methods for chromatin biology

2014

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Next generation sequencing (NGS) technologies have been used in diverse ways to investigate facets of chromatin biology by identifying genomic loci that are bound by transcription factors, occupied by nucleosomes, accessible to nuclease cleavage, or physically interact with remote genomic loci. Reaching sound biological conclusions from such NGS enrichment profiles, however, requires that many potential biases be taken into account. In this Review we discuss common ways in which bias may be introduced into NGS chromatin profiling data, ways in which these biases can be diagnosed, and analytical techniques to mitigate their effect.

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“…Large-scale, systematic efforts to perform ChIP with carefully validated antibodies in multiple cell lines have generated an invaluable resource for the genomics community [43,44]. Histone modification ChIP data are useful for both identification of regulatory elements [45] more generally as an input to computational strategies for determining chromatin states [46,47]. TF ChIP data sets have been fed into TF binding motif databases [48–50] and combined with open chromatin data to create genome-wide maps of presumptive TF binding in cell lines where individual TF ChIP experiments were not necessarily performed [8,30].…”

Section: Primary Structurementioning

confidence: 99%

Unraveling the 3D genome: genomics tools for multiscale exploration

Risca

Greenleaf

2015

Trends in Genetics

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A decade of rapid method development has begun to yield exciting insights into the three-dimensional architecture of the metazoan genome and the roles it may play in regulating transcription. We review here core methods and new tools in the modern genomicist’s toolbox at three length scales, ranging from single base pair to megabase scale chromosomal domains, and discuss the emerging picture of the 3D genome that these tools have revealed. Blind spots remain, especially at intermediate length scales spanning a few nucleosomes, but thanks in part to new technologies that permit targeted alteration of chromatin states and time-resolved studies, the next decade holds great promise for hypothesis-driven research into the mechanisms that drive genome architecture and transcriptional regulation.

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Unsupervised pattern discovery in human chromatin structure through genomic segmentation

Cited by 568 publications

References 33 publications

Human Promoters Are Intrinsically Directional

Human Promoters Are Intrinsically Directional

Identifying and mitigating bias in next-generation sequencing methods for chromatin biology

Unraveling the 3D genome: genomics tools for multiscale exploration

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