A spatial and temporal map of <i>C. elegans</i> gene expression

Spencer, W. Clay; Zeller, Georg; Watson, Joseph D.; Henz, Stefan R.; Watkins, Kathie L.; McWhirter, Rebecca; Petersen, Sarah C.; Sreedharan, Vipin T.; Widmer, Christian; Jo, Jeanyoung; Reinke, V; Petrella, Lisa N.; Strome, Susan; Stetina, Stephen E. Von; Katz, Mark N.; Shaham, Shai; Rätsch, Gunnar; Miller, David M.

doi:10.1101/gr.114595.110

Cited by 264 publications

(350 citation statements)

References 105 publications

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“…An interesting approach to overcome this difficulty is to FACS-sort embryonic cells expressing the right markers (Spencer et al, 2011;Bonn et al, 2012;Zhou and Pu, 2012). This way, it is possible to obtain accurate temporal maps of chromatin changes.…”

Section: Perspectivesmentioning

confidence: 99%

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Frankel

2012

Developmental Dynamics

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Genomes contain the necessary information to ensure that genes are expressed in the right place, at the right time, and with the proper rate. Metazoan developmental genes often possess long stretches of DNA flanking their coding sequences and/or large introns which contain elements that influence gene expression. Most of these regulatory elements are relatively small and can be studied in isolation. For example, transcriptional enhancers, the elements that generate the expression pattern of a gene, have been traditionally studied with reporter constructs in transgenic animals. These studies have provided and will provide invaluable insights into enhancer evolution and function. However, this experimental approach has its limits; often, enhancer elements do not faithfully recapitulate native expression patterns. This fact suggests that additional information in cis-regulatory regions modulates the activity of enhancers and other regulatory elements. Indeed, recent studies have revealed novel functional aspects at the level of whole cis-regulatory regions. First, the discovery of ''shadow enhancers.'' Second, the ubiquitous interactions between cis-regulatory elements. Third, the notion that some cis-regulatory regions may not function in a modular manner. Last, the effect of chromatin conformation on cis-regulatory activity. In this article, I describe these recent findings and discuss open questions in the field.

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Section: Perspectivesmentioning

confidence: 99%

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Frankel

2012

Developmental Dynamics

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“…6C; Spencer et al 2011;Gerstein et al 2014;Pérez-Lluch et al 2015). We hypothesized that if promoter nucleosome fragility is related to context-specific expression as our GO analysis suggested, then we should find higher fragility signals near developmentally regulated genes.…”

Section: Nucleosome Fragility Is Not Associated With a Specific Epigementioning

confidence: 99%

“…Prenormalized transcriptome sequencing data were downloaded from: https://www.encodeproject.org/comparative/transcriptome/ (Spencer et al 2011;Gerstein et al 2014). For each gene, we calculated the coefficient of variation (CV): c v = σ/μ.…”

Section: Stable and Developmentally Regulated Genesmentioning

confidence: 99%

Nucleosome fragility is associated with future transcriptional response to developmental cues and stress inC. elegans

Jeffers

Lieb

2016

Genome Res.

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Nucleosomes have structural and regulatory functions in all eukaryotic DNA-templated processes. The position of nucleosomes on DNA and the stability of the underlying histone-DNA interactions affect the access of regulatory proteins to DNA. Both stability and position are regulated through DNA sequence, histone post-translational modifications, histone variants, chromatin remodelers, and transcription factors. Here, we explored the functional implications of nucleosome properties on gene expression and development in Caenorhabditis elegans embryos. We performed a time-course of micrococcal nuclease (MNase) digestion and measured the relative sensitivity or resistance of nucleosomes throughout the genome. Fragile nucleosomes were defined by nucleosomal DNA fragments that were recovered preferentially in early MNase-digestion time points. Nucleosome fragility was strongly and positively correlated with the AT content of the underlying DNA sequence. There was no correlation between promoter nucleosome fragility and the levels of histone modifications or histone variants. Genes with fragile nucleosomes in their promoters tended to be lowly expressed and expressed in a contextspecific way, operating in neuronal response, the immune system, and stress response. In addition to DNA-encoded nucleosome fragility, we also found fragile nucleosomes at locations where we expected to find destabilized nucleosomes, for example, at transcription factor binding sites where nucleosomes compete with DNA-binding factors. Our data suggest that in C. elegans promoters, nucleosome fragility is in large part DNA-encoded and that it poises genes for future context-specific activation in response to environmental stress and developmental cues.[Supplemental material is available for this article.]The fundamental unit of eukaryotic chromatin is the nucleosome, which consists of 147 bp of DNA wrapped around an octamer of histone proteins (Luger et al. 1997). Nucleosomes have important structural and regulatory functions in organizing the genome and restricting access of regulatory factors to the DNA sequence (Henikoff 2008). As such, the interactions between nucleosomes and DNA strongly influence the regulation of gene expression by determining DNA accessibility for transcription factors (TFs) and RNA polymerase. In addition to regulated nucleosome assembly and disassembly through the action of histone chaperones and chromatin remodelers, nucleosome stability is influenced by histone modifications, histone variants, DNA features encoded in cis, and competition with DNA-binding factors in trans . A complete picture of the mechanisms governing nucleosome stability is fundamental to understanding how gene expression is dynamically regulated.Nucleosome stability has been studied in vitro using sensitivity to enzymatic digestion or salt concentration (Bloom and Anderson 1978;Burton et al. 1978;Li et al. 1993;Polach and Widom 1995;Wu and Travers 2004;Jin and Felsenfeld 2007). Genome-wide adaptations of these methods have been used to identify nuc...

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“…14). These SOM have long been used for analysis of gene-expression (15,16) and chromatin data (17) because they can resolve relationships in very large datasets with large numbers of clusters, and here they provide an elegant way to identify multiple, related modules of Bcl11b targets with distinct roles in development. In fact, many of the new Bcl11b target genes are unique to the pericommitment developmental context.…”

mentioning

confidence: 99%

Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network

Longabaugh

Zeng

Zhang

et al. 2017

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

148

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T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment and relate them to other regulomes. We show that both activation and repression target genes can be bound by Bcl11b in vivo, and that Bcl11b effects overlap with E2A-dependent effects. The newly clarified role of Bcl11b distinguishes discrete components of commitment, resolving how innate lymphoid, myeloid, and dendritic, and B-cell fate alternatives are excluded by different mechanisms.

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A spatial and temporal map of C. elegans gene expression

Cited by 264 publications

References 105 publications

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Nucleosome fragility is associated with future transcriptional response to developmental cues and stress inC. elegans

Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network

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