The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Remodeling of the Enhancer Landscape during Macrophage Activation Is Coupled to Enhancer Transcription
Open accessAbstract
Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell-type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of ∼3,000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and dimethylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4, and Mll3 and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts.
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“Several studies have shown that the level of eRNA transcription correlates with enhancer activity [60,61].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [60]
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“Within cell-specific enhancers, DNA sequences provide information about the identities of key LDTFs and the activity states of signaling pathways that control the functions of SDTFs (31, 33–35).”
From An environment-dependent transcriptional network specifies human microglia identity (2017) · cites this paper as [33]
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“In untreated macrophages, H3K27ac was enriched both at the promoter region of Tet2 and a region lying 40kb upstream, thus constituting a putative distal enhancer element (Figure 2A).”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Kaikkonen et al., 2013
Experimental — accuracy not yet measuredIn the citing paper
“Immune memory in microglia and macrophages are shaped by epigenetically mediated alterations in the enhancer repertoire of targeted genes [11, 32].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [32]
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Citations
Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
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Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling
Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. S., & Weissman, J. S. (2009) · Science · doi:10.1126/science.1168978 · Cited by 3,853
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002) · Science · doi:10.1126/science.1076997 · Cited by 3,775
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“, high enrichment of histone H3 lysine 4 mono- and dimethylation (H3K4me1 and H3K4me2, respectively) and low enrichment of H3K4me3 compared to promoters (Heintzman et al., 2007).”
BackgroundThe accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679
Histone modifications at human enhancers reflect global cell-type-specific gene expression
Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450
A unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233
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Trained immunity: A program of innate immune memory in health and– disease
Netea, M. G., Joosten, L. A. B., Latz, E., Mills, K. H. G., Natoli, G., Stunnenberg, H. G., O’Neill, L. A. J., & Xavier, R. J. (2016) · Science · doi:10.1126/science.aaf1098 · Cited by 2,768
Gosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.023 · Cited by 1,307
An environment-dependent transcriptional network specifies human microglia identity
Gosselin, D., Skola, D., Coufal, N. G., Holtman, I. R., Schlachetzki, J. C. M., Sajti, E., Jaeger, B. N., O’Connor, C., Fitzpatrick, C., Pasillas, M. P., et al. (2017) · Science · doi:10.1126/science.aal3222 · Cited by 1,220
Innate immune memory in the brain shapes neurological disease hallmarks
Wendeln, A.-C., Degenhardt, K., Kaurani, L., Gertig, M., Ulas, T., Jain, G., Wagner, J., Häsler, L. M., Wild, K., Skodras, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0023-4 · Cited by 956
The selection and function of cell type-specific enhancers
Heinz, S., Romanoski, C. E., Benner, C., & Glass, C. K. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3949 · Cited by 1,010
Self-citation
Metadata
- Authors
- Kaikkonen, M. U., Spann, N. J., Heinz, S., Romanoski, C. E., Allison, K. A., Stender, J. D., Chun, H. B., Tough, D. F., Prinjha, R. K., Benner, C., & Glass, C. K.
- Affiliations
- University of Eastern Finland (FI)
- University of California San Diego (US)
- GlaxoSmithKline (United Kingdom) (GB)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Glass, Christopher K.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 51
- Issue
- 3
- Pages
- 310-325
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3779836
- OpenAlex
- W1998871958
- Cited by
- 672
- References
- 63
- Citations by year
- 2026: 26 · 2025: 36 · 2024: 43 · 2023: 35 · 2022: 52 · 2021: 56 · 2020: 50 · 2019: 46 · 2018: 69 · 2017: 73 · 2016: 61 · 2015: 66 · 2014: 48 · 2013: 11
- FWCI
- 27.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Fondation Leducq
- Academy of Finland
- Suomen Kulttuurirahasto
- Sydäntutkimussäätiö
- National Institutes of Health
- National Cancer Institute (R01CA173903, CA17390)
- National Institute of General Medical Sciences (T32GM008806)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, DK091183, P01DK074868, P30DK063491, R01DK091183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- enhancer remodeling, macrophage activation, enhancer transcription, TLR4 signaling, H3K4 methylation, MLL1, MLL3, RNA polymerase II elongation, enhancer RNA, histone methyltransferase
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Base Sequence, Cells, Cultured, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Histones, Macrophage Activation, Macrophages, Male, Mice, Inbred C57BL, Histone-Lysine N-Methyltransferase, Proto-Oncogene Proteins, RNA Polymerase II, Transcription, Genetic, Signal Transduction, Trans-Activators, Gene Expression, NF-kappa B, Sequence Analysis, DNA, DNA Methylation, CCAAT-Enhancer-Binding Proteins, Toll-Like Receptor 4, Mice, Myeloid-Lymphoid Leukemia Protein, Transcription Factor RelA
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