A Unifying Model for the Selective Regulation of Inducible Transcription By CpG Islands and Nucleosome Remodeling

By V. Ramirez-Carrozzi, D. Braas, Dev Bhatt, Christine S Cheng, C. Hong, K. Doty, Joshua C. Black, Alexander Hoffmann, M. Carey, S. Smale. Cell, 2009

597 citations recorded by the source corpus.

SUMMARY We describe a broad mechanistic framework for the transcriptional induction of mammalian primary response genes by Toll-like receptors and other stimuli. One major class of primary response genes is characterized by CpG-island promoters, which facilitate promiscuous induction from constitutively active chromatin without a requirement for SWI/SNF nucleosome remodeling complexes. The low nucleosome occupancy at promoters in this class can be attributed to the assembly of CpG islands into unstable nucleosomes, which may lead to SWI/SNF independence. Another major class consists of non-CpG-island promoters that assemble into stable nucleosomes, resulting in SWI/SNF dependence and a requirement for transcription factors that promote selective nucleosome remodeling. Some stimuli, including serum and tumor necrosis factor-α, exhibit a strong bias toward activation of SWI/SNF-independent CpG-island genes. In contrast, interferon-β is strongly biased toward SWI/SNF-dependent non-CpG-island genes. By activating a diverse set of transcription factors, Toll-like-receptors induce both classes and others for an optimal response to microbial pathogens.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9bbfbe56515a99bc1ec5f99ba967f8967f190b4c

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Citations in the corpus

Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. (2010, background): “Importantly, genes associated with enhancers bound by p300 in an LPSinducible manner belonged to several classes of LPS-responsive genes (primary, secondary, promiscuously, and selectively activated genes) (Ramirez-Carrozzi et al., 2009), without any obvious specificity.”
Parsing the interferon transcriptional network and its disease associations (2016, unknown): “…is a relative dearth of CpG islands around the TSS of these genes (19% vs 47% genomewide, p= 2×10 − 5 ), in keeping with the results of Carrozzi et al (Ramirez-Carrozzi et al., 2009) who showed that many ISGs belong to a class of inducible genes that require SWI/SNF-dependent nucleosome remodeling…”
A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers (2010, methodology): “Conversely, the system used in this study has the advantage that genes are induced in a kinetically complex fashion [73,74], in Non-Coding Transcription at Enhancers”
DNA Methylation and Its Basic Function (2013, background): “One of the common features of CpG islands is that they contain less nucleosomes than other stretches of DNA (Tazi and Bird, 1990; Ramirez-Carrozzi et al, 2009; Choi, 2010).”
Latent enhancers activated by stimulation in differentiated cells. (2013, unknown): “Once the STAT TF are bound they may recruit Pu.1 and together stabilize the open and accessible state by recruiting chromatin-remodelers (Cui et al., 2004; Huang et al., 2002; Liu et al., 2002), as demonstrated at the promoters of inflammatory genes (Ramirez-Carrozzi et al., 2009).”
SWI/SNF nucleosome remodellers and cancer (2011, background): “In studies looking for general principles that govern inducible gene expression using interferon-β induction as a model, it was found that SWI/SNF complexes are required for the specific regulation of interferon-β target”
Distinct factors control histone variant H3.3 localization at specific genomic regions (2010, background): “Most HCP genes show evidence of transcriptional initiation, assemble unstable nucleosomes, and do not require SWI/ SNF nucleosome remodeling complexes for gene induction, while LCP genes assemble stable nucleosomes and require SWI/SNF (Guenther et al., 2007; Ramirez-Carrozzi et al., 2009).”
Feedback regulation of EGFR signalling: decision making by early and delayed loops (2011, background): “Their CpG islands act as nucleosome destabilizers, enabling transcriptional activators such as SP1 to gain access to the promoters and recruit Pol II in the uninduced state, without the need for nucleosome remodellin”
Transcriptional regulation of macrophage polarization: enabling diversity with identity (2011, background): “The promoters of most primary response genes involved in the initial response to LPS stimulation — such as those encoding tumour necrosis factor (TNF), superoxide dismutase 2 (SOD2) and prostaglandin G/H synthase 2 (PTGS2) — contain CpG island”
NF-κB Signaling in Macrophages: Dynamics, Crosstalk, and Signal Integration (2019, background): “For example, NF-κB activation can arise through the stimulation of many cytokine receptors like TNFRs and IL1Rs (23), PRRs such as TLRs (24), MAVS (25), STING (26), and NOD-like receptors (27), as well as T and B cell receptors (28, 29), among many others.”
DNA methylation and cancer. (2010, background): “…response genes by Toll-like receptors revealed the possible role of nucleosome density at different types of promoters (containing CGI or not) (Ramirez-Carrozzi et al., 2009). target genes by either degradation or translational inhibition. miRNAs act as tumorsuppressors if they target…”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “Indeed, recent studies in macrophages and ES cells have documented roles for specific transcription factors in regulating steps downstream of initiatio”
Trained immunity: a program of innate immune memory in health and disease (2016, background): “In myeloid cells, many loci encoding inflammatory genes are in a repressed configuration (66-68), as inferred by their limited accessibility to nucleases (used as tools to probe chromatin structure), the low acetylation of the nucleosomal histones, and the very low amount of RNA polymerase II loaded”
Signaling via the NFκB system (2016, background): “These pathways tightly control the levels and dynamics of the transcriptionally active NFκB dimer repertoire constitutively and in response to stimuli, and thus control broad gene expression programs(15,16) via the recruitment of co-activators(17) or interplay with other transcription factors.(18,19”