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A map of the cis-regulatory sequences in the mouse genome
Open accessAbstract
The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 × 10(9) bases of the mouse genome possess a high degree of conservation with the human genome, so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences, but on its own it cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including humans, Drosophila melanogaster and Caenorhabditis elegans. Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.
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“Furthermore, an analysis of publically available DNase I hypersensitivity data (Shen et al., 2012) confirmed that >60% of embryonic sites remain accessible in the adult liver (data not shown).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Shen et al., 2012
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BackgroundYY1 and CTCF orchestrate a 3D chromatin looping switch during early neural lineage commitment
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“Changes in the levels of expression of genes appeared to be correlated within TADs during cell differentiation (Nora et al. 2012), potentially by topologically constraining enhancer or silencer activity (Symmons et al. 2014).”
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Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation
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Self-citationThe histone chaperone CAF-1 safeguards somatic cell identity
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“The upper data tracks (yellow) show POL2, CTCF and chromatin modification marks from the Encode project (Consortium, 2012; Shen et al., 2012).”
BackgroundTissueEnrich: Tissue-specific gene enrichment analysis
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Chromatin States in Mouse Sperm Correlate with Embryonic and Adult Regulatory Landscapes
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“Using these criteria, we find 10,240 THSSs that correspond to previously characterized enhancers in embryonic or adult tissues (Figure 3B) (Shen et al., 2012).”
MethodPrinciples of regulatory information conservation between mouse and human
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“Enhancers are critical regulatory elements required for the tight developmental and tissue specific regulation of gene expression and hence it is not surprising that the number of enhancers in mammalian genome far exceeds the number of protein coding genes [57, 58].”
BackgroundNkx2-1 Represses a Latent Gastric Differentiation Program in Lung Adenocarcinoma
Snyder, E. L., Watanabe, H., Magendantz, M., Hoersch, S., Chen, T. A., Wang, D. G., Crowley, D. G., Whittaker, C. A., Meyerson, M. M., Kimura, S., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.02.018 · Cited by 259
“The greatest number of epigenetic changes induced by Nkx2-1 deletion occurred in the H3K4me1 and H3K27ac modifications (Figure 5D and S5D), consistent with reports that these modifications correlate more closely with differentiation state than others (Creyghton et al., 2010; Shen et al., 2012).”
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“Peaks were further filtered as described previously (Shen et al., 2012).”
MethodSelf-citationNeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program
Pataskar, A., Jung, J., Smialowski, P., Noack, F., Calegari, F., Straub, T., & Tiwari, V. K. (2015) · The EMBO Journal · doi:10.15252/embj.201591206 · Cited by 285
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Self-citationANP32E is a histone chaperone that removes H2A.Z from chromatin
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Long-Range Chromatin Interactions
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“Chromatin looping interactions between genes and their regulatory elements occurs mostly within TADs, which is perhaps not surprising given that chromatin interactions between TADs, in general, are of lower frequency (Sanyal et al. 2012; Shen et al. 2012).”
BackgroundRole of Tet proteins in enhancer activity and telomere elongationPreprint
Lu, F., Liu, Y., Jiang, L., Yamaguchi, S., & Zhang, Y. (2014) · Genes & Development · doi:10.1101/gad.248005.114 · Cited by 278
“…(5hmC) (Tahiliani et al. 2009; Ito et al. 2010), which in turn can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) and then excised by TDG followed by base excision repair to complete the demethylation cycle (He et al. 2011; Ito et al. 2011; Shen et al. 2013).”
BackgroundInfluentialInterferon-γ induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation
Yu, M., Peng, Z., Qin, M., Liu, Y., Wang, J., Zhang, C., Lin, J., Dong, T., Wang, L., Li, S., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.01.010 · Cited by 250
Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells
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“Indeed, DHMRs that showed gain of 5hmC in Tet2 kd mESC were enriched for Tet1 binding sites (21), which tend to be present at regions of DNase I hypersensitivity that bear histone marks associated with promoters and active enhancers (H3K4me2, H3K4me3 and H3K27Ac) (22) (Fig.”
MethodA statistical approach for inferring the 3D structure of the genome
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Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition
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“By comparing the genomic localization of MLL4 with those of Oct4, Sox2, and Nanog (O/S/N) and the H3K27 acetyltransferase p300 that marks AEs (4, 9), we found that MLL4 colocalized with O/S/N and p300 on AEs (Fig.”
BackgroundEnhancer variants: evaluating functions in common disease
Corradin, O., & Scacheri, P. C. (2014) · Genome Medicine · doi:10.1186/s13073-014-0085-3 · Cited by 241
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CTCF: the protein, the binding partners, the binding sites and their chromatin loops
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“…the chromatin state of regions with accessibility changes, we used ChromHMM 36 to establish a chromatin state model defined by recurrent combinations of histone modifications using the ChIP-seq dataset from the adult mouse hippocampus 27 and CTCF ChIP-seq dataset from the adult mouse cortex 28 .”
Active DNA demethylation at enhancers during the vertebrate phylotypic period
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Self-citationChromatin Insulators: Linking Genome Organization to Cellular Function
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“Two recent genome-wide analyses have provided new insights that now prompt us to re-evaluate the role for EB mechanisms in mammalian systems (Sanyal et al., 2012; Shen et al., 2012).”
BackgroundExtensive identification and analysis of conserved small ORFs in animals
Mackowiak, S. D., Zauber, H., Bielow, C., Thiel, D., Kutz, K., Calviello, L., Mastrobuoni, G., Rajewsky, N., Kempa, S., Selbach, M., et al. (2015) · Genome Biology · doi:10.1186/s13059-015-0742-x · Cited by 227
“For the expression analysis of sORF-containing transcripts we used RNA-seq data for 16 human tissues (Illumina Body Map), for 19 mouse tissues [103], for eight developmental stages of zebrafish [98], 24 developmental stages for fruit fly from modENCODE, and eight developmental stages in C.”
MethodEnhancer Function: Mechanistic and Genome-Wide Insights Come Together
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Identification of alternative topological domains in chromatin
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“For mouse embryonic cell CTCF binding sites and chromatin modification marks, we used data by Shen et al. [19].”
MethodSymmons, O., Pan, L., Remeseiro, S., Aktas, T., Klein, F., Huber, W., & Spitz, F. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.10.015 · Cited by 222
“ChIP-Seq tracks from CH12 cells (Shen et al., 2012) as well as from embryonic limbs (forelimb – FL, hindlimb HL) indicate CTCF and the cohesin subunit SMC1 (Demare et al., 2013).”
BackgroundBetancur, P. A., Abraham, B. J., Yiu, Y. Y., Willingham, S. B., Khameneh, F., Zarnegar, M. A., Kuo, A. H., McKenna, K. M., Kojima, Y., Leeper, N. J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14802 · Cited by 243
“…Paired-End Tag (ChIA-PET) data 22,23 confirmed that E5 and the downstream CD47 SE in MCF7 are connected by a DNA loop containing RNA Polymerase II, part of the complex of factors that are necessary to initiate transcription and are associated with promoter regions 22,24,25 (Supplementary Fig.”
Identification of active regulatory regions from DNA methylation data
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Bayesian Inference of Spatial Organizations of Chromosomes
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Self-citationThe Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb
Cotney, J. L., Leng, J., Yin, J., Reilly, S. K., DeMare, L. E., Emera, D., Ayoub, A. E., RAKIC, P. T., & Noonan, J. P. (2013) · Cell · doi:10.1016/j.cell.2013.05.056 · Cited by 215
Insights into epigenetic patterns in mammalian early embryos
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“…cells (e.g., ENCODE Project Consortium 2012; Muerdter et al. 2018) compared with ∼15,000 expressed genes (Ramsköld et al. 2009), between 200,000 and 300,000 across ∼20 mouse tissues (Shen et al. 2012; Yue et al. 2014), and ∼400,000 across a set of 127 cell lines (ENCODE Project Consortium 2012).”
BackgroundThe long non‐coding RNA Paupar regulates the expression of both local and distal genes
Vance, K. W., Sansom, S. N., Lee, S., Chalei, V., Kong, L., Cooper, S., Oliver, P. L., & Ponting, C. P. (2014) · The EMBO Journal · doi:10.1002/embj.201386225 · Cited by 213
CRISPR Reveals a Distal Super-Enhancer Required for Sox2 Expression in Mouse Embryonic Stem Cells
Li, Y., Rivera, C. M., Ishii, H., Jin, F., Selvaraj, S., Lee, A. Y., Dixon, J. R., & Ren, B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114485 · Cited by 212
Self-citationCoBATCH for High-Throughput Single-Cell Epigenomic Profiling
Wang, Q., Xiong, H., Ai, S., Yu, X., Liu, Y., Zhang, J., & He, A. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.015 · Cited by 213
TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling
Dai, H.-Q., Wang, B.-A., Yang, L., Chen, J.-J., Zhu, G.-C., Sun, M.-L., Ge, H., Wang, R., Chapman, D. L., Tang, F., et al. (2016) · Nature · doi:10.1038/nature20095 · Cited by 206
Evolution of transcription factor binding in metazoans — mechanisms and functional implications
Villar, D., Flicek, P., & Odom, D. T. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3481 · Cited by 217
DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress
Yao, B., Cheng, Y., Wang, Z., Li, Y., Chen, L., Huang, L., Zhang, W., Chen, D., Wu, H., Tang, B., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01195-y · Cited by 217
Batut, P. J., Dobin, A., Plessy, C., Carninci, P., & Gingeras, T. (2012) · Genome Research · doi:10.1101/gr.139618.112 · Cited by 205
“…started to shed light on the abundance of cis-regulatory modules (Ernst et al. 2011; Negre et al. 2011; The ENCODE Project Consortium et al. 2012; Shen et al. 2012), their relevance to development and disease (Lindblad-Toh et al. 2011; The ENCODE Project Consortium et al. 2012), and the…”
BackgroundBosse, K. R., Raman, P., Zhu, Z., Lane, M. V., Martínez, D., Heitzeneder, S., Rathi, K. S., Kendsersky, N. M., Randall, M. P., Donovan, L., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.08.003 · Cited by 226
“Importantly, the similar mouse and human GPC2 expression profile (Figures 1C and S8F) (Shen et al., 2012), coupled with the equal binding of this ADC to mouse and human GPC2 (Figure 7B), suggests murine models provide a valid assessment of the potential for D3-GPC2-PBD on-target, off-tumor toxicities.”
ResultA common genetic variant within SCN10A modulates cardiac SCN5A expression
van den Boogaard, M., Smemo, S., Burnicka-Turek, O., Arnolds, D. E., van de Werken, H. J. G., Klous, P., McKean, D. M., Muehlschlegel, J. D., Moosmann, J., Toka, O., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci73140 · Cited by 192
“We aligned 4C-seq with cardiac ChIP-seq data for TBX3 (21) as well as for Pol2 and p300 (27–29) to visualize interactions for EnhA and EnhB (Figure 1C).”
MethodTaylor, G. C. A., Eskeland, R., Hekimoglu-Balkan, B., Pradeepa, M. M., & Bickmore, W. A. (2013) · Genome Research · doi:10.1101/gr.155028.113 · Cited by 203
“Gene histone mark average profiles were generated using custom perl scripts and the coverageBed utility of the BEDTools suite, and normalized to RPM/bp. H4K16ac peak localization throughout the genome was analyzed using the CEAS suite (Shin et al. 2009).”
MethodGenetic Approaches to Neural Circuits in the Mouse
Josh Huang, Z., & Zeng, H. (2013) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062012-170307 · Cited by 200
An Overview of Genome Organization and How We Got There: from FISH to Hi-C
Fraser, J., Williamson, I., Bickmore, W. A., & Dostie, J. (2015) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00006-15 · Cited by 232
“This model is supported by the fact that partitioning of the genome into TADs correlates with enhancer-promoter units, clusters of coregulated promoters and enhancers (179, 311).”
MethodChromatin as dynamic 10-nm fibers
Maeshima, K., Imai, R., Tamura, S., & Nozaki, T. (2014) · Chromosoma · doi:10.1007/s00412-014-0460-2 · Cited by 218
Spatially resolved epigenomic profiling of single cells in complex tissues
Lu, T., Ang, C. E., & Zhuang, X. (2022) · Cell · doi:10.1016/j.cell.2022.09.035 · Cited by 197
Jia, G., Preussner, J., Chen, X. X., Günther, S., Yuan, X., Yekelchyk, M., Kuenne, C. T., Looso, M., Zhou, Y., Teichmann, S. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07307-6 · Cited by 219
CoBATCH for high-throughput single-cell epigenomic profilingPreprint
Wang, Q., Xiong, H., Ai, S.-S., Yu, X.-H., Liu, Y., Zhang, J., & He, A. (2019) · bioRxiv · doi:10.1101/590661 · Cited by 194
Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation
Yu, B., Zhang, K., Milner, J. J., Toma, C., Chen, R., Scott-Browne, J. P., Pereira, R. M., Crotty, S., Chang, J. T., Pipkin, M. E., et al. (2017) · Nature Immunology · doi:10.1038/ni.3706 · Cited by 248
A Sox2 distal enhancer cluster regulates embryonic stem cell differentiation potential
Zhou, H. Y., Katsman, Y., Dhaliwal, N. K., Davidson, S., Macpherson, N. N., Sakthidevi, M., Collura, F., & Mitchell, J. A. (2014) · Genes & Development · doi:10.1101/gad.248526.114 · Cited by 192
“In addition, the insulator-binding protein CCCTC-binding factor (CTCF), a protein involved in anchoring chromatin–chromatin interactions, is bound within both the distal region and the promoter-proximal region (Phillips and Corces 2009; Shen et al. 2012).”
Liu, X., Xu, J., Rosenthal, S., Zhang, L., McCubbin, R., Meshgin, N., Shang, L., Koyama, Y., Ma, H., Sharma, S., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.027 · Cited by 208
Dynamic epigenomic landscapes during early lineage specification in mouse embryos
Zhang, Y., Xiang, Y., Yin, Q., Du, Z., Xu, P., Wang, Q., Fidalgo, M., Xia, W., Li, Y., Zhao, Z., et al. (2017) · Nature Genetics · doi:10.1038/s41588-017-0003-x · Cited by 217
Evaluating Enhancer Function and Transcription
Field, A. R., & Adelman, K. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-011420-095916 · Cited by 227
“Notably, many genes appear to be influenced by multiple discrete enhancer loci (15, 16).”
BackgroundChromatin organization and transcriptional regulation
Hübner, M. R., Eckersley-Maslin, M. A., & Spector, D. L. (2012) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2012.11.006 · Cited by 186
PU.1 controls fibroblast polarization and tissue fibrosis
Wohlfahrt, T., Rauber, S., Uebe, S., Luber, M., Soare, A., Ekici, A., Weber, S., Matei, A.-E., Chen, C.-W., Maier, C., et al. (2019) · Nature · doi:10.1038/s41586-019-0896-x · Cited by 187
“For region of interest (ROI)-based ChIP-seq peak and RNA-seq overlap analysis, ROI were defined as 225kb upstream and downstream of differentially expressed genes 65 .”
Dynamics of 5-hydroxymethylcytosine during mouse spermatogenesis
Gan, H., Wen, L., Liao, S., Lin, X., Ma, T., Liu, J., Song, C., Wang, M., He, C., Han, C., et al. (2013) · Nature Communications · doi:10.1038/ncomms2995 · Cited by 203
An atlas of gene regulatory elements in adult mouse cerebrum
Li, Y. E., Preissl, S., Hou, X., Zhang, Z., Zhang, K., Qiu, Y., Poirion, O. B., Li, B., Chiou, J., Liu, H., et al. (2021) · Nature · doi:10.1038/s41586-021-03604-1 · Cited by 185
Self-citationEnhancing Hi-C data resolution with deep convolutional neural network HiCPlus
Zhang, Y., An, L., Xu, J., Zhang, B., Zheng, W. J., Hu, M., Tang, J., & Yue, F. (2018) · Nature Communications · doi:10.1038/s41467-018-03113-2 · Cited by 189
Self-citationGlobal discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation
Alvarez‐Dominguez, J. R., Hu, W., Yuan, B., Shi, J., Park, S. S., Gromatzky, A. A., van Oudenaarden, A., & Lodish, H. F. (2013) · Blood · doi:10.1182/blood-2013-10-530683 · Cited by 189
“To classify the repertoire of fetal liver lncRNAs, we examined their overlap with annotated genes 18-20 or enhancers 21 (Figure 1C) and systematically assigned them to lncRNA classes (supplemental Figure 1D; supplemental Methods).”
High-throughput genome scaffolding from in vivo DNA interaction frequency
Kaplan, N., & Dekker, J. (2013) · Nature Biotechnology · doi:10.1038/nbt.2768 · Cited by 177
Histone propionylation is a mark of active chromatin
Kebede, A. F., Nieborak, A., Shahidian, L. Z., Gras, S. L., Richter, F. M., Aguilar‐Gómez, D., Baltissen, M. P. A., Mészáros, G., Magliarelli, H. D. F., Taudt, A., et al. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3490 · Cited by 215
Yang, Y. J., Baltus, A. E., Mathew, R. S., Murphy, E. A., Evrony, G. D., Gonzalez, D. M., Wang, E. P., Marshall-Walker, C. A., Barry, B. J., Murn, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.043 · Cited by 176
“C ZNF335 interacts with a methyltransferase complex, we looked at the methylation patterns of these ZNF335-bound promoters (Shen et al., 2012), and the peaks of ZNF335 binding overlapped with the H3K4 trimethylation (H3K4me3) peaks (Figure S5A).”
BackgroundSpatially resolved epigenomic profiling of single cells in complex tissuesPreprint
Lu, T., Ang, C., & Zhuang, X.-W. (2022) · bioRxiv · doi:10.1101/2022.02.17.480825 · Cited by 176
“…been identified in both embryonic and adult brains (Gorkin et al., 2020; Gray et al., 2017; Graybuck et al., 2021; Mo et al., 2015; Preissl et al., 2018; Shen et al., 2012; Visel et al., 2009, 2013; Yue et al., 2014), but the detailed spatial distributions remain unclear for most of these elements.”
How to rule the nucleus: divide et impera
Solovei, I. V., Thanisch, K., & Feodorova, Y. N. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.02.014 · Cited by 198
Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation
Tsagaratou, A., Äijö, T., Lio, C. J., Yue, X., Huang, Y., Jacobsen, S. E., Lähdesmäki, H. J., & Rao, A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412327111 · Cited by 186
“5 kb of the reported enhancer center positions (35).”
BackgroundEvolutionary conservation of the eumetazoan gene regulatory landscapePreprint
Schwaiger, M., Schönauer, A., Rendeiro, A. F., Pribitzer, C., Schauer, A., Gilles, A. F., Schinko, J. B., Renfer, E., Fredman, D., & Technau, U. (2014) · Genome Research · doi:10.1101/gr.162529.113 · Cited by 191
“…catalyzes the acetylation of histones, the transcriptional cofactor EP300 (also known as p300), has been shown to bind to enhancers, and has recently been used in several studies to predict enhancer elements genome wide (Visel et al. 2009b; May et al. 2011; Nègre et al. 2011; Shen et al. 2012).”
BackgroundInfluentialUniform, optimal signal processing of mapped deep-sequencing data
Kumar, V., Muratani, M., Rayan, N. A., Kraus, P., Lufkin, T., Ng, H., & Prabhakar, S. (2013) · Nature Biotechnology · doi:10.1038/nbt.2596 · Cited by 161
A comparative atlas of single-cell chromatin accessibility in the human brain
Li, Y. E., Preissl, S., Miller, M., Johnson, N. D., Wang, Z., Jiao, H., Zhu, C., Wang, Z., Xie, Y., Poirion, O., et al. (2023) · Science · doi:10.1126/science.adf7044 · Cited by 173
“Current catalogs of candidate regulatory sequences in the human genome, most notably those generated by the ENCODE andEpigenomeRoadmap consortia (6, 7, 18, 19), still lack the information about cell-type–specific activities of each element, especially those identified from brain tissues, because conventional assays pe…”
BackgroundSelf-citationSong, M., Yang, X., Ren, X., Maliskova, L., Li, B., Jones, I. R., Wang, C., Jacob, F., Wu, K., Traglia, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0472-1 · Cited by 167
“2a), consistent with the large number of regulatory elements in the human genome 22 and previous findings that promoters can be regulated by multiple enhancers 23 .”
Self-citationIn search of the determinants of enhancer–promoter interaction specificity
van Arensbergen, J., van Steensel, B., & Bussemaker, H. J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.004 · Cited by 180
“In an alternative, but conceptually similar approach, yielding similar conclusions, the chromatin state of enhancers was correlated with that of promoters in order to identify functional enhancer–promoter pairs [29].”
ResultSegmental folding of chromosomes: A basis for structural and regulatory chromosomal neighborhoods?
Nora, E. P., Dekker, J., & Heard, É. (2013) · BioEssays · doi:10.1002/bies.201300040 · Cited by 187
Modeling gene regulation from paired expression and chromatin accessibility data
Duren, Z., Chen, X., Jiang, R., Wang, Y., & Wong, W. (2017) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1704553114 · Cited by 171
Locus-Specific Targeting to the X Chromosome Revealed by the RNA Interactome of CTCF
Kung, J. T., Kesner, B., An, J. Y., Ahn, J. Y., Cifuentes‐Rojas, C., Colognori, D., Jeon, Y., Szántó, A., Rosario, B. C. D., Pinter, S. F., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2014.12.006 · Cited by 180
Marques, A. C., Hughes, J. R., Graham, B., Kowalczyk, M. S., Higgs, D. R., & Ponting, C. P. (2013) · Genome biology · doi:10.1186/gb-2013-14-11-r131 · Cited by 178
“A relatively high level of H3K4me1- over H3K4me3modified chromatin is a well-established property of enhancers [20,34,35] that has been extensively used to generate genome-wide catalogues of enhancer- or promoterlike regulatory elements [36].”
Background
Metadata
- Authors
- Shen, Y., Yue, F., McCleary, D. F., Ye, Z., Edsall, L., Kuan, S., Wagner, U., Dixon, J., Lee, L., Lobanenkov, V. V., & Ren, B.
- Affiliations
- Ludwig Cancer Research (US)
- University of California San Diego (US)
- National Institutes of Health (US)
- Corresponding author
- Ren, Bing
- ORCID
- Venue
- Nature
- Published
- 2012-07-01
- Volume
- 488
- Issue
- 7409
- Pages
- 116-120
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4041622
- OpenAlex
- W2042930277
- Cited by
- 1,361
- References
- 29
- Citations by year
- 2026: 12 · 2025: 24 · 2024: 51 · 2023: 75 · 2022: 88 · 2021: 119 · 2020: 90 · 2019: 107 · 2018: 97 · 2017: 110 · 2016: 125 · 2015: 137 · 2014: 167 · 2013: 132 · 2012: 26
- FWCI
- 59.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Human Genome Research Institute (R01HG003991)
- National Institute of General Medical Sciences (T32GM007198)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- cis-regulatory sequences, mouse genome, enhancers, promoter, CTCF binding sites, tissue-specific gene expression, transcription factor binding, conserved non-coding elements, genome annotation, ChIP-seq
- MeSH terms
- Acetylation, Animals, Chromatin, Enhancer Elements, Genetic, Gene Expression Regulation, Male, Methylation, Mice, Inbred C57BL, Organ Specificity, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription Factors, Genome, Conserved Sequence, Sequence Analysis, DNA, Evolution, Molecular, Physical Chromosome Mapping, Chromatin Immunoprecipitation, Mice, Molecular Sequence Annotation, Nucleotide Motifs
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