IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29261-0.html
   My bibliography  Save this article

Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin

Author

Listed:
  • Carlos Rivera

    (Pontificia Universidad Católica de Chile
    Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Hun-Goo Lee

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Anna Lappala

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Danni Wang

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Verónica Noches

    (Pontificia Universidad Católica de Chile)

  • Montserrat Olivares-Costa

    (Pontificia Universidad Católica de Chile)

  • Marcela Sjöberg-Herrera

    (Pontificia Universidad Católica de Chile)

  • Jeannie T. Lee

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • María Estela Andrés

    (Pontificia Universidad Católica de Chile)

Abstract

RCOR1 is a known transcription repressor that recruits and positions LSD1 and HDAC1/2 on chromatin to erase histone methylation and acetylation. However, there is currently an incomplete understanding of RCOR1’s range of localization and function. Here, we probe RCOR1’s distribution on a genome-wide scale and unexpectedly find that RCOR1 is predominantly associated with transcriptionally active genes. Biochemical analysis reveals that RCOR1 associates with RNA Polymerase II (POL-II) during transcription and deacetylates its carboxy-terminal domain (CTD) at lysine 7. We provide evidence that this non-canonical RCOR1 activity is linked to dampening of POL-II productive elongation at actively transcribing genes. Thus, RCOR1 represses transcription in two ways—first, via a canonical mechanism by erasing transcriptionally permissive histone modifications through associating with HDACs and, second, via a non-canonical mechanism that deacetylates RNA POL-II’s CTD to inhibit productive elongation. We conclude that RCOR1 is a transcription rheostat.

Suggested Citation

  • Carlos Rivera & Hun-Goo Lee & Anna Lappala & Danni Wang & Verónica Noches & Montserrat Olivares-Costa & Marcela Sjöberg-Herrera & Jeannie T. Lee & María Estela Andrés, 2022. "Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29261-0
    DOI: 10.1038/s41467-022-29261-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29261-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29261-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jason Ernst & Pouya Kheradpour & Tarjei S. Mikkelsen & Noam Shoresh & Lucas D. Ward & Charles B. Epstein & Xiaolan Zhang & Li Wang & Robbyn Issner & Michael Coyne & Manching Ku & Timothy Durham & Mano, 2011. "Mapping and analysis of chromatin state dynamics in nine human cell types," Nature, Nature, vol. 473(7345), pages 43-49, May.
    2. Jay H. Kalin & Muzhou Wu & Andrea V. Gomez & Yun Song & Jayanta Das & Dawn Hayward & Nkosi Adejola & Mingxuan Wu & Izabela Panova & Hye Jin Chung & Edward Kim & Holly J. Roberts & Justin M. Roberts & , 2018. "Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    3. Jakub Mieczkowski & April Cook & Sarah K. Bowman & Britta Mueller & Burak H. Alver & Sharmistha Kundu & Aimee M. Deaton & Jennifer A. Urban & Erica Larschan & Peter J. Park & Robert E. Kingston & Mich, 2016. "MNase titration reveals differences between nucleosome occupancy and chromatin accessibility," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    4. Tianyi Zhang & Guifeng Wei & Christopher J. Millard & Roman Fischer & Rebecca Konietzny & Benedikt M. Kessler & John W. R. Schwabe & Neil Brockdorff, 2018. "A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Seungsoo Hahn & Dongsup Kim, 2015. "Identifying and Reducing Systematic Errors in Chromosome Conformation Capture Data," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-17, December.
    3. Ye Cai & Huifen Cao & Fang Wang & Yufei Zhang & Philipp Kapranov, 2022. "Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    4. Chirag Nepal & Jesper B. Andersen, 2023. "Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Haoxi Chai & Harianto Tjong & Peng Li & Wei Liao & Ping Wang & Chee Hong Wong & Chew Yee Ngan & Warren J. Leonard & Chia-Lin Wei & Yijun Ruan, 2023. "ChIATAC is an efficient strategy for multi-omics mapping of 3D epigenomes from low-cell inputs," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Zhangyuan Pan & Yuelin Yao & Hongwei Yin & Zexi Cai & Ying Wang & Lijing Bai & Colin Kern & Michelle Halstead & Ganrea Chanthavixay & Nares Trakooljul & Klaus Wimmers & Goutam Sahana & Guosheng Su & M, 2021. "Pig genome functional annotation enhances the biological interpretation of complex traits and human disease," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    7. Maurizio Mangolini & Alba Maiques-Diaz & Stella Charalampopoulou & Elena Gerhard-Hartmann & Johannes Bloehdorn & Andrew Moore & Giorgia Giachetti & Junyan Lu & Valar Nila Roamio Franklin & Chandra Sek, 2022. "Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    8. Noah Dukler & Mehreen R. Mughal & Ritika Ramani & Yi-Fei Huang & Adam Siepel, 2022. "Extreme purifying selection against point mutations in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Ting Shen & Ting Ni & Jiaxuan Chen & Haitao Chen & Xiaopin Ma & Guangwen Cao & Tianzhi Wu & Haisheng Xie & Bin Zhou & Gang Wei & Hexige Saiyin & Suqin Shen & Peng Yu & Qianyi Xiao & Hui Liu & Yuzheng , 2022. "An enhancer variant at 16q22.1 predisposes to hepatocellular carcinoma via regulating PRMT7 expression," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Julia Truch & Damien J. Downes & Caroline Scott & E. Ravza Gür & Jelena M. Telenius & Emmanouela Repapi & Ron Schwessinger & Matthew Gosden & Jill M. Brown & Stephen Taylor & Pak Leng Cheong & Jim R. , 2022. "The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. Rachel K. Lex & Weiqiang Zhou & Zhicheng Ji & Kristin N. Falkenstein & Kaleigh E. Schuler & Kathryn E. Windsor & Joseph D. Kim & Hongkai Ji & Steven A. Vokes, 2022. "GLI transcriptional repression is inert prior to Hedgehog pathway activation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Nina Schmolka & Ino D. Karemaker & Richard Cardoso da Silva & Davide C. Recchia & Vincent Spegg & Jahnavi Bhaskaran & Michael Teske & Nathalie P. Wagenaar & Matthias Altmeyer & Tuncay Baubec, 2023. "Dissecting the roles of MBD2 isoforms and domains in regulating NuRD complex function during cellular differentiation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Zhaoyun Ding & Ting Cai & Jupei Tang & Hanxiao Sun & Xinyi Qi & Yunpeng Zhang & Yan Ji & Liyun Yuan & Huidan Chang & Yanhui Ma & Hong Zhou & Li Li & Huiming Sheng & Ju Qiu, 2022. "Setd2 supports GATA3+ST2+ thymic-derived Treg cells and suppresses intestinal inflammation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    14. Jennifer P. Nguyen & Timothy D. Arthur & Kyohei Fujita & Bianca M. Salgado & Margaret K. R. Donovan & Hiroko Matsui & Ji Hyun Kim & Agnieszka D’Antonio-Chronowska & Matteo D’Antonio & Kelly A. Frazer, 2023. "eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    15. Carlos Olmeda-Gómez & Carlos Romá-Mateo & Maria-Antonia Ovalle-Perandones, 2019. "Overview of trends in global epigenetic research (2009–2017)," Scientometrics, Springer;Akadémiai Kiadó, vol. 119(3), pages 1545-1574, June.
    16. Chaitali Chakraborty & Itzel Nissen & Craig A. Vincent & Anna-Carin Hägglund & Andreas Hörnblad & Silvia Remeseiro, 2023. "Rewiring of the promoter-enhancer interactome and regulatory landscape in glioblastoma orchestrates gene expression underlying neurogliomal synaptic communication," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Mijeong Kim & Shili Lin, 2020. "Characterization of histone modification patterns and prediction of novel promoters using functional principal component analysis," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-16, May.
    18. Xintao Qiu & Nadia Boufaied & Tarek Hallal & Avery Feit & Anna Polo & Adrienne M. Luoma & Walaa Alahmadi & Janie Larocque & Giorgia Zadra & Yingtian Xie & Shengqing Gu & Qin Tang & Yi Zhang & Sudeepa , 2022. "MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    19. M S Vijayabaskar & Debbie K Goode & Nadine Obier & Monika Lichtinger & Amber M L Emmett & Fatin N Zainul Abidin & Nisar Shar & Rebecca Hannah & Salam A Assi & Michael Lie-A-Ling & Berthold Gottgens & , 2019. "Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets," PLOS Computational Biology, Public Library of Science, vol. 15(11), pages 1-29, November.
    20. Mary F Feitosa & Aldi T Kraja & Daniel I Chasman & Yun J Sung & Thomas W Winkler & Ioanna Ntalla & Xiuqing Guo & Nora Franceschini & Ching-Yu Cheng & Xueling Sim & Dina Vojinovic & Jonathan Marten & S, 2018. "Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries," PLOS ONE, Public Library of Science, vol. 13(6), pages 1-36, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29261-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.