Native Elongating Transcript Sequencing Reveals Human Transcriptional Activity at Nucleotide Resolution

Mayer, Andreas; di Iulio, Julia; Maleri, Seth; Eser, Umut; Vierstra, Jeff; Reynolds, Alex; Sandstrom, Richard; Stamatoyannopoulos, John A.; Churchman, L. Stirling

doi:10.1016/j.cell.2015.03.010

Cited by 369Genomics and Chromatin DynamicsRNA Research and SplicingCancer-related molecular mechanisms research

Native Elongating Transcript Sequencing Reveals Human Transcriptional Activity at Nucleotide Resolution

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Mayer, Andreas, di Iulio, Julia, Maleri, Seth, Eser, Umut, Vierstra, Jeff, Reynolds, Alex, Sandstrom, Richard, Stamatoyannopoulos, John A. +1 more·2015·Cell

DOI 10.1016/j.cell.2015.03.010PMC PMC4528962

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Abstract

Major features of transcription by human RNA polymerase II (Pol II) remain poorly defined due to a lack of quantitative approaches for visualizing Pol II progress at nucleotide resolution. We developed a simple and powerful approach for performing native elongating transcript sequencing (NET-seq) in human cells that globally maps strand-specific Pol II density at nucleotide resolution. NET-seq exposes a mode of antisense transcription that originates downstream and converges on transcription from the canonical promoter. Convergent transcription is associated with a distinctive chromatin configuration and is characteristic of lower-expressed genes. Integration of NET-seq with genomic footprinting data reveals stereotypic Pol II pausing coincident with transcription factor occupancy. Finally, exons retained in mature transcripts display Pol II pausing signatures that differ markedly from skipped exons, indicating an intrinsic capacity for Pol II to recognize exons with different processing fates. Together, human NET-seq exposes the topography and regulatory complexity of human gene expression.

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In mammals and many other metazoans, promoter-proximal pausing occurs 25-50 base pairs downstream from the TSS and is a major rate-limiting step of the transcription cycle.
“In mammals and many other metazoans, promoter‐proximal pausing occurs 25–50 base pairs downstream from the TSS and is a major rate‐limiting step of the transcription cycle (Jonkers et al, 2014; Mayer et al, 2015).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Mayer et al, 2015
The Introduction reports strong promoter-proximal pauses about 50 bp downstream of many transcription start sites. The Results describe release of paused Pol II as important for productive elongation, but the paper does not establish that pausing is a major rate-limiting step of the transcription cycle across mammals and other metazoans, or specify a 25–50 bp range. (LLM, conf=0.86)
Experimental — accuracy not yet measured
PRO-seq and NET-seq confirmed a pause at the 3′ splice site in budding yeast and Drosophila, at the 3′ and 5′ splice sites in human cells, and at the 5′ splice site in plants.
“These methods also confirmed the existence of a pause at the 3′ splice site in budding yeast (Harlen et al, 2016) and Drosophila (Kwak et al, 2013), at the 3′ and 5′ splice sites in human cells (Mayer et al, 2015; Nojima et al, 2015) and at the 5′ splice site in plants (Kindgren et al, 2020).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Mayer et al, 2015
Higher RNA Pol II accumulation has been reported at spliced exons, as compared to skipped exons.
“Moreover, higher RNA Pol II accumulation has been reported at spliced exons, as compared to skipped exons (Kwak et al, 2013; Mayer et al, 2015; Nojima et al, 2015).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Mayer et al, 2015

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Hitting the ‘mark’: Interpreting lysine methylation in the context of active transcription
Wozniak, G. G., & Strahl, B. D. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.002 · Cited by 82 · see citing works
Convergent transcription induces transcriptional gene silencing in fission yeast and mammalian cells
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Coupling transcription factor occupancy to nucleosome architecture with DNase-FLASH
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“Jump Start and Gain” Model for Dosage Compensation in Drosophila Based on Direct Sequencing of Nascent Transcripts
Ferrari, F., Plachetka, A., Alekseyenko, A. A., Jung, Y. L., Ozsolak, F., Kharchenko, P. V., Park, P. J., & Kuroda, M. I. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.09.037 · Cited by 40 · see citing works
Considering the kinetics of mRNA synthesis in the analysis of the genome and epigenome reveals determinants of co-transcriptional splicing
Davis‐Turak, J., Allison, K. A., Shokhirev, M. N., Ponomarenko, P. M., Tsimring, L. S., Glass, C. K., Johnson, T., & Hoffmann, A. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1338 · Cited by 19 · see citing works

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Determinants of enhancer and promoter activities of regulatory elements
Andersson, R., & Sandelin, A. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0173-8 · Cited by 713 · see citing works
<i>N</i> <sup>6</sup> -methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription
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Enhancers as non-coding RNA transcription units: recent insights and future perspectives
Li, W., Notani, D., & Rosenfeld, M. G. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.4 · Cited by 710 · see citing works
RNA ‐Seq methods for transcriptome analysis
Hrdličková, R., Toloue, M., & Tian, B. (2016) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1364 · Cited by 686 · see citing works
Promoter-proximal pausing of RNA polymerase II: a nexus of gene regulationPreprint
Core, L. J., & Adelman, K. (2019) · Genes & Development · doi:10.1101/gad.325142.119 · Cited by 560 · see citing works
TT-seq maps the human transient transcriptome
Schwalb, B., Michel, M., Zacher, B., Frühauf, K., Demel, C., Tresch, A., Gagneur, J., & Cramer, P. (2016) · Science · doi:10.1126/science.aad9841 · Cited by 548 · see citing works
Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals
Sanz, L. A., Hartono, S. R., Lim, Y. W., Steyaert, S., Rajpurkar, A. R., Ginno, P. A., Xu, X., & Chedin, F. L. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.032 · Cited by 560 · see citing works
Base-pair-resolution genome-wide mapping of active RNA polymerases using precision nuclear run-on (PRO-seq)
Mahat, D. B., Kwak, H., Booth, G. T., Jonkers, I. H., Danko, C. G., Patel, R. K., Waters, C. T., Munson, K. M., Core, L. J., & Lis, J. T. (2016) · Nature Protocols · doi:10.1038/nprot.2016.086 · Cited by 492 · see citing works
The code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain
Harlen, K. M., & Churchman, L. S. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.10 · Cited by 499 · see citing works
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Improved CUT&RUN chromatin profiling tools
Meers, M. P., Bryson, T. D., Henikoff, J. G., & Henikoff, S. (2019) · eLife · doi:10.7554/elife.46314 · Cited by 474 · see citing works
BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment
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Single Mammalian Cells Compensate for Differences in Cellular Volume and DNA Copy Number through Independent Global Transcriptional Mechanisms
Padovan-Merhar, O. M., Nair, G. P., Biaesch, A. G., Mayer, A., Scarfone, S., Foley, S. W., Wu, A. R., Churchman, L. S., Singh, A., & Raj, A. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.03.005 · Cited by 434 · see citing works
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Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics
Nojima, T., & Proudfoot, N. J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00447-6 · Cited by 424 · see citing works
Regulation of Co-transcriptional Pre-mRNA Splicing by m6A through the Low-Complexity Protein hnRNPG
Zhou, K. I., Shi, H., Lyu, R., Wylder, A. C., Matuszek, Ż., Pan, J. N., He, C., Parisien, M., & Pan, T. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.005 · Cited by 385 · see citing works
R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters
Chen, L., Chen, J., Zhang, X., Gu, Y., Xiao, R., Shao, C., Tang, P., Qian, H., Luo, D., Li, H., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.008 · Cited by 373 · see citing works
Splicing and transcription touch base: co-transcriptional spliceosome assembly and function
Herzel, L., Ottoz, D. S. M., Alpert, T., & Neugebauer, K. M. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.63 · Cited by 356 · see citing works
Architectural and Functional Commonalities between Enhancers and Promoters
Kim, T.-K., & Shiekhattar, R. (2015) · Cell · doi:10.1016/j.cell.2015.08.008 · Cited by 331 · see citing works
Distinctive Patterns of Transcription and RNA Processing for Human lincRNAs
Schlackow, M., Nojima, T., Gomes, T., Dhir, A., Carmo‐Fonseca, M., & Proudfoot, N. J. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.11.029 · Cited by 295 · see citing works
Coupling of RNA Polymerase II Transcription Elongation with Pre-mRNA Splicing
Saldi, T. K., Cortázar, M. A., Sheridan, R. M., & Bentley, D. L. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.04.017 · Cited by 246 · see citing works
Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation
Gates, L. A., Shi, J., Rohira, A. D., Feng, Q. F., Zhu, B., Bedford, M. T., Sagum, C. A., Jung, S. Y., Qin, J., Tsai, M., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.802074 · Cited by 247 · see citing works
Nascent RNA analyses: tracking transcription and its regulation
Wissink, E. M., Vihervaara, A., Tippens, N. D., & Lis, J. T. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0159-6 · Cited by 247 · see citing works
Causes and consequences of RNA polymerase II stalling during transcript elongation
González, M. N., Blears, D., & Svejstrup, J. Q. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00308-8 · Cited by 238 · see citing works
CDK9-dependent RNA polymerase II pausing controls transcription initiation
Gressel, S., Schwalb, B., Decker, T.-M., Qin, W., Leonhardt, H., Eick, D., & Cramer, P. (2017) · eLife · doi:10.7554/elife.29736 · Cited by 239 · see citing works
Splicing Kinetics and Coordination Revealed by Direct Nascent RNA Sequencing through Nanopores
Drexler, H. L., Choquet, K., & Churchman, L. S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.11.017 · Cited by 234 · see citing works
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CDK9: a signaling hub for transcriptional control
Bacon, C. W., & D’Orso, I. (2018) · Transcription · doi:10.1080/21541264.2018.1523668 · Cited by 201 · see citing works
RNA polymerase II speed: a key player in controlling and adapting transcriptome composition
Muniz, L., Nicolas, E., & Trouche, D. (2021) · The EMBO Journal · doi:10.15252/embj.2020105740 · Cited by 203 · see citing works
“…showed that RNA Pol II accumulates on exons in yeast and human, suggesting that RNA Pol II pauses over exons (Brodsky et al , 2005; Schwartz et al , 2009; Alexander et al , 2010; Carrillo Oesterreich et al , 2010; Kwak et al , 2013; Mayer et al , 2015; Nojima et al , 2015; Harlen et al , 2016).”
Influential
Sequence determinants of human gene regulatory elements
Sahu, B., Hartonen, T., Pihlajamaa, P., Wei, B., Dave, K., Zhu, F., Kaasinen, E., Lidschreiber, K., Lidschreiber, M., Daub, C. O., et al. (2022) · Nature Genetics · doi:10.1038/s41588-021-01009-4 · Cited by 198 · see citing works
UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene
Williamson, L. M., Saponaro, M., Boeing, S., East, P., Mitter, R., Kantidakis, T., Kelly, G. P., Lobley, A., Walker, J., Spencer‐Dene, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.01.019 · Cited by 197 · see citing works
Co-transcriptional splicing regulates 3′ end cleavage during mammalian erythropoiesis
Reimer, K. A., Mimoso, C. A., Adelman, K., & Neugebauer, K. M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.018 · Cited by 180 · see citing works
R-Loops Promote Antisense Transcription across the Mammalian Genome
Tan‐Wong, S. M., Dhir, S., & Proudfoot, N. J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.10.002 · Cited by 164 · see citing works
Transcriptional response to stress is pre-wired by promoter and enhancer architecture
Vihervaara, A., Mahat, D. B., Guertin, M. J., Chu, T., Danko, C. G., Lis, J. T., & Sistonen, L. (2017) · Nature Communications · doi:10.1038/s41467-017-00151-0 · Cited by 164 · see citing works
Comprehensive RNA Polymerase II Interactomes Reveal Distinct and Varied Roles for Each Phospho-CTD Residue
Harlen, K. M., Trotta, K. L., Smith, E. E., Mosaheb, M. M., Fuchs, S. M., & Churchman, L. S. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.010 · Cited by 150 · see citing works
Self-citation
Post-transcriptional splicing of nascent RNA contributes to widespread intron retention in plants
Jia, J., Long, Y., Zhang, H., Li, Z., Liu, Z., Zhao, Y., Lu, D., Jin, X., Deng, X. M., Xia, R., et al. (2020) · Nature Plants · doi:10.1038/s41477-020-0688-1 · Cited by 140 · see citing works
Insights into the biogenesis and potential functions of exonic circular RNA
Ragan, C., Goodall, G. J., Shirokikh, N. E., & Preiss, T. (2019) · Scientific Reports · doi:10.1038/s41598-018-37037-0 · Cited by 137 · see citing works
Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme
Chu, T., Rice, E. J., Booth, G. T., Salamanca, H. H., Wang, Z., Core, L. J., Longo, S. L., Corona, R. J., Chin, L. S., Lis, J. T., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0244-3 · Cited by 129 · see citing works
The essential and multifunctional TFIIH complex
Rimel, J. K., & Taatjes, D. J. (2018) · Protein Science · doi:10.1002/pro.3424 · Cited by 137 · see citing works
Anything but Ordinary – Emerging Splicing Mechanisms in Eukaryotic Gene Regulation
Gehring, N. H., & Roignant, J. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.10.008 · Cited by 134 · see citing works
Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb
Quaresma, A. J. C., Bugai, A., & Barborič, M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw585 · Cited by 131 · see citing works
A Two-Way Street: Regulatory Interplay between RNA Polymerase and Nascent RNA Structure
Zhang, J., & Landick, R. C. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.12.009 · Cited by 129 · see citing works
Pause & go: from the discovery of RNA polymerase pausing to its functional implications
Mayer, A., Landry, H. M., & Churchman, L. S. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.03.002 · Cited by 125 · see citing works
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Transcriptional Pause Sites Delineate Stable Nucleosome-Associated Premature Polyadenylation Suppressed by U1 snRNP
Chiu, A., Suzuki, H. I., Wu, X., Mahat, D. B., Kriz, A. J., & Sharp, P. A. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.006 · Cited by 124 · see citing works
Kethoxal-assisted single-stranded DNA sequencing captures global transcription dynamics and enhancer activity in situ
Wu, T., Lyu, R., You, Q., & He, C. (2020) · Nature Methods · doi:10.1038/s41592-020-0797-9 · Cited by 115 · see citing works
Single-molecule nascent RNA sequencing identifies regulatory domain architecture at promoters and enhancers
Tome, J. M., Tippens, N. D., & Lis, J. T. (2018) · Nature Genetics · doi:10.1038/s41588-018-0234-5 · Cited by 112 · see citing works
NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements
Hirabayashi, S., Bhagat, S., Matsuki, Y., Takegami, Y., Uehata, T., Kanemaru, A., Itoh, M., Shirakawa, K., Takaori‐Kondo, A., Takeuchi, O., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0485-9 · Cited by 109 · see citing works
Using TTchem-seq for profiling nascent transcription and measuring transcript elongation
Gregersen, L. H., Mitter, R., & Svejstrup, J. Q. (2020) · Nature Protocols · doi:10.1038/s41596-019-0262-3 · Cited by 117 · see citing works
7SK-BAF axis controls pervasive transcription at enhancers
Flynn, R. A., Do, B. T., Rubin, A. J., Calo, E., Lee, B., Kuchelmeister, H. Y., Rale, M. J., Chu, C., Kool, E. T., Wysocka, J., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3176 · Cited by 112 · see citing works
Identification of regulatory elements from nascent transcription using dREGPreprint
Wang, Z., Chu, T., Choate, L. A., & Danko, C. G. (2018) · Genome Research · doi:10.1101/gr.238279.118 · Cited by 108 · see citing works
Enhanced Identification of Transcriptional Enhancers Provides Mechanistic Insights into Diseases
Murakawa, Y., Yoshihara, M., Kawaji, H., Nishikawa, M., Zayed, H., Suzuki, H., & Hayashizaki, Y. (2016) · Trends in Genetics · doi:10.1016/j.tig.2015.11.004 · Cited by 111 · see citing works
Native elongation transcript sequencing reveals temperature dependent dynamics of nascent RNAPII transcription in Arabidopsis
Kindgren, P., Ivanov, M., & Marquardt, S. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1189 · Cited by 113 · see citing works
Long-read sequencing of nascent RNA reveals coupling among RNA processing eventsPreprint
Herzel, L., Straube, K., & Neugebauer, K. M. (2018) · Genome Research · doi:10.1101/gr.232025.117 · Cited by 107 · see citing works
Mammalian NET-seq analysis defines nascent RNA profiles and associated RNA processing genome-wide
Nojima, T., Gomes, T., Carmo‐Fonseca, M., & Proudfoot, N. J. (2016) · Nature Protocols · doi:10.1038/nprot.2016.012 · Cited by 111 · see citing works
Long-Distance Cooperative and Antagonistic RNA Polymerase Dynamics via DNA Supercoiling
Kim, S., Beltran, B. G., Irnov, I., & Jacobs, C. (2019) · Cell · doi:10.1016/j.cell.2019.08.033 · Cited by 106 · see citing works
MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes
Boxer, L. D., Renthal, W. R., Greben, A. W., Whitwam, T., Silberfeld, A., Stroud, H., Li, E., Yang, M. G., Kinde, B., Griffith, E. C., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.10.032 · Cited by 111 · see citing works
RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD Phosphorylation, and Transcriptional Direction
Fong, N., Saldi, T., Sheridan, R. M., Cortazar, M. A., & Bentley, D. L. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.016 · Cited by 98 · see citing works
Intragenic Enhancers Attenuate Host Gene Expression
Cinghu, S., Yang, P., Kosak, J. P., Conway, A. E., Kumar, D., Oldfield, A. J., Adelman, K., & Jothi, R. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.010 · Cited by 100 · see citing works
Perfect timing: splicing and transcription rates in living cells
Alpert, T., Herzel, L., & Neugebauer, K. M. (2017) · WIREs RNA · doi:10.1002/wrna.1401 · Cited by 99 · see citing works
POINT technology illuminates the processing of polymerase-associated intact nascent transcripts
Sousa‐Luís, R., Dujardin, G., Zukher, I., Kimurâ, H., Weldon, C., Carmo‐Fonseca, M., Proudfoot, N. J., & Nojima, T. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.02.034 · Cited by 94 · see citing works
RNA Binding Proteins RZ-1B and RZ-1C Play Critical Roles in Regulating Pre-mRNA Splicing and Gene Expression during Development in Arabidopsis
Wu, Z., Zhu, D., Lin, X., Miao, J., Gu, L., Deng, X. M., Yang, Q., Sun, K., Zhu, D., Cao, X., et al. (2015) · The Plant Cell · doi:10.1105/tpc.15.00949 · Cited by 93 · see citing works
P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress
Bugai, A., Quaresma, A. J. C., Friedel, C. C., Lenasi, T., Düster, R., Sibley, C. R., Fujinaga, K., Kukanja, P., Hennig, T., Blasius, M., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.033 · Cited by 90 · see citing works
Co-transcriptional gene regulation in eukaryotes and prokaryotes
Shine, M., Gordon, J. M., Schärfen, L., Zigáčková, D., Herzel, L., & Neugebauer, K. M. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00706-2 · Cited by 95 · see citing works
Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation
Shetty, A., Kallgren, S. P., Demel, C., Maier, K. C., Spatt, D., Alver, B. H., Cramer, P., Park, P. J., & Winston, F. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.023 · Cited by 91 · see citing works
Cellular Fractionation and Isolation of Chromatin-Associated RNA
Conrad, T., & Ørom, U. A. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-4035-6_1 · Cited by 90 · see citing works
Mechanisms of Transcriptional Pausing in Bacteria
Kang, J. Y., Mishanina, T. V., Landick, R. C., & Darst, S. A. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.07.017 · Cited by 90 · see citing works
Transcription and splicing: A two‐way street
Tellier, M., Maudlin, I., & Murphy, S. (2020) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1593 · Cited by 82 · see citing works
Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding
Kadota, S.-I., Ou, J.-H., Shi, Y., Lee, J. T., Sun, J., & Yildirim, E. (2020) · Nature Communications · doi:10.1038/s41467-020-16394-3 · Cited by 15 · see citing works
Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals
Shah, N., Maqbool, M. A., Yahia, Y., Aabidine, A. Z. E., Esnault, C., Forné, I., Decker, T.-M., Martin, D. P., Schüller, R., Krebs, S., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2017.12.009 · Cited by 84 · see citing works
Oxidative stress rapidly stabilizes promoter-proximal paused Pol II across the human genome
Nilson, K. A., Lawson, C. K., Mullen, N. J., Ball, C. B., Spector, B. M., Meier, J. L., & Price, D. H. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx724 · Cited by 85 · see citing works
The Ground State and Evolution of Promoter Region Directionality
Jin, Y., Eser, U., Struhl, K., & Churchman, L. S. (2017) · Cell · doi:10.1016/j.cell.2017.07.006 · Cited by 79 · see citing works
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Architecture and RNA binding of the human negative elongation factor
Vos, S. M., Pöllmann, D., Caizzi, L., Hofmann, K., Rombaut, P., Zimniak, T., Herzog, F., & Cramer, P. (2016) · eLife · doi:10.7554/elife.14981 · Cited by 78 · see citing works
Nascent RNA and the Coordination of Splicing with TranscriptionPreprint
Neugebauer, K. M. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032227 · Cited by 77 · see citing works
Distinct properties and functions of CTCF revealed by a rapidly inducible degron system
Luan, J. Y., Xiang, G., Gómez-García, P. A., Tome, J. M., Zhang, Z., Vermunt, M. W., Zhang, H., Huang, A., Keller, C. A., Giardine, B. M., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108783 · Cited by 81 · see citing works
Global donor and acceptor splicing site kinetics in human cells
Wachutka, L., Caizzi, L., Gagneur, J., & Cramer, P. (2019) · eLife · doi:10.7554/elife.45056 · Cited by 77 · see citing works
Enhancer and super‐enhancer: Positive regulators in gene transcription
Peng, Y., & Zhang, Y. (2018) · Animal Models and Experimental Medicine · doi:10.1002/ame2.12032 · Cited by 74 · see citing works
The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture
Pai, A. A., Henriques, T., McCue, K., Burkholder, A., Adelman, K., & Burge, C. B. (2017) · eLife · doi:10.7554/elife.32537 · Cited by 78 · see citing works
Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters
Chen, Y., Pai, A. A., Herudek, J., Lubas, M., Meola, N., Järvelin, A. I., Andersson, R., Pelechano, V., Steinmetz, L. M., Jensen, T. H., et al. (2016) · Nature Genetics · doi:10.1038/ng.3616 · Cited by 78 · see citing works
Natural temperature fluctuations promote COOLAIR regulation of FLCPreprint
Zhao, Y., Zhu, P., Hepworth, J., Bloomer, R. H., Antoniou-Kourounioti, R. L., Doughty, J., Heckmann, A., Xu, C., Yang, H., & Dean, C. (2021) · Genes & Development · doi:10.1101/gad.348362.121 · Cited by 78 · see citing works
Nascent Transcript Folding Plays a Major Role in Determining RNA Polymerase Elongation Rates
Turowski, T. W., Petfalski, E., Goddard, B. D., French, S. L., Helwak, A., & Tollervey, D. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.06.002 · Cited by 75 · see citing works
A BRD4-mediated elongation control point primes transcribing RNA polymerase II for 3′-processing and termination
Arnold, M., Bressin, A., Jasnovidova, O., Meierhofer, D., & Mayer, A. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.06.026 · Cited by 75 · see citing works
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Regulatory feedback from nascent RNA to chromatin and transcription
Skalska, L., Beltran-Nebot, M., Ule, J., & Jenner, R. G. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.12 · Cited by 71 · see citing works
Cell-Size-Dependent Transcription of FLC and Its Antisense Long Non-coding RNA COOLAIR Explain Cell-to-Cell Expression Variation
Ietswaart, R., Rosa, S., Wu, Z., Dean, C., & Howard, M. (2017) · Cell Systems · doi:10.1016/j.cels.2017.05.010 · Cited by 73 · see citing works
Regulatory mechanisms of incomplete huntingtin mRNA splicing
Neueder, A., Dumas, A. A., Benjamin, A. C., & Bates, G. P. (2018) · Nature Communications · doi:10.1038/s41467-018-06281-3 · Cited by 74 · see citing works
Alternative polyadenylation mediates genetic regulation of gene expression
Mittleman, B. E., Pott, S., Warland, S., Zeng, T., Mu, Z., Kaur, M., Gilad, Y., & Li, Y. (2020) · eLife · doi:10.7554/elife.57492 · Cited by 69 · see citing works
Spt6 Is Required for the Fidelity of Promoter Selection
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High Resolution Architecture of Human Transcriptional Activity Revealed by Native Elongating Transcript Sequencing
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Authors: Mayer, A., di Iulio, J., Maleri, S., Eser, U., Vierstra, J., Reynolds, A., Sandstrom, R., Stamatoyannopoulos, J. A., & Churchman, L. S.
Affiliations: Harvard University (US)
University of Washington (US)
Corresponding author: Churchman, L. Stirling
ORCID: Mayer, Andreas
Vierstra, Jeff
Reynolds, Alex
Sandstrom, Richard
Stamatoyannopoulos, John A.
Churchman, L. Stirling
Venue: Cell
Publisher: Elsevier BV
Published: 2015-04
Volume: 161
Issue: 3
Pages: 541-554
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2015.03.010
PMC: PMC4528962
OpenAlex: W2037429489
Cited by: 367
References: 86
Citations by year: 2026: 15 · 2025: 19 · 2024: 24 · 2023: 30 · 2022: 37 · 2021: 40 · 2020: 36 · 2019: 39 · 2018: 32 · 2017: 39 · 2016: 38 · 2015: 16
FWCI: 18.10
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 388 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Human Genome Research Institute (U54HG007010, R01HG007173)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords: RNA polymerase II, transcription elongation, antisense transcription, convergent transcription, transcription factor occupancy, genomic footprinting, exon skipping
MeSH terms: Enhancer Elements, Genetic, Exons, HeLa Cells, Humans, Promoter Regions, Genetic, RNA Polymerase II, Transcription Factors, Transcription, Genetic, RNA, Antisense, Alternative Splicing, Sequence Analysis, RNA, Transcription Elongation, Genetic

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Native Elongating Transcript Sequencing Reveals Human Transcriptional Activity at Nucleotide Resolution

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