A Role for Nuclear Actin in HDAC 1 and 2 Regulation
Open accessAbstract
Class I histone deacetylases (HDACs) are known to remove acetyl groups from histone tails. This liberates positive charges on the histone tail and allows for tighter winding of DNA, preventing transcription factor binding and gene activation. Although the functions of HDAC proteins are becoming apparent both biochemically and clinically, how this class of proteins is regulated remains poorly understood. We identified a novel interaction between nuclear actin and HDAC 1 and HDAC 2. Nuclear actin has been previously shown to interact with a growing list of nuclear proteins including chromatin remodeling complexes, transcription factors and RNA polymerases. We find that monomeric actin is able to bind the class I HDAC complex. Furthermore, increasing the concentration of actin in HeLa nuclear extracts was able to suppress overall HDAC function. Conversely, polymerizing nuclear actin increased HDAC activity and decreased histone acetylation. Moreover, the interaction between class I HDACs and nuclear actin was found to be activity dependent. Together, our data suggest nuclear actin is able to regulate HDAC 1 and 2 activity.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Specific nuclear events and gene transcription are regulated by the availability of monomeric actin, since various nuclear proteins, such as chromatin remodeling complexes, histone modifiers and RNA polymerases, require monomeric actin for their activity.
“Notably, specific nuclear events and gene transcription are regulated by the availability of monomeric actin, since various nuclear proteins, such as chromatin remodeling complexes88, histone modifiers89 and RNA polymerases90,91, require monomeric actin for their activity.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [89]
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Weintraub, H., & Groudine, M. (1976) · Science · doi:10.1126/science.948749 · Cited by 1,809 · see citing works
Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes
Wang, Z., Zang, C., Cui, K., Schones, D. E., Barski, A., Peng, W., & Zhao, K. (2009) · Cell · doi:10.1016/j.cell.2009.06.049 · Cited by 1,344 · see citing works
Delcuve, G. P., Khan, D. H., & Davie, J. R. (2012) · Clinical Epigenetics · doi:10.1186/1868-7083-4-5 · Cited by 505 · see citing works
The functional interactome landscape of the human histone deacetylase family
Joshi, P., Greco, T. M., Guise, A. J., Luo, Y., Yu, F., Nesvizhskii, A. I., & Cristea, I. M. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.26 · Cited by 289 · see citing works
Flagged first, then by citations
Research works printed but not linked: 50
- Dokmanovic M., Clarke C. & Marks P. A. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 5, 981– 9 (2007). 17951399
- Yang X. J. & Seto E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 26, 5310– 8 (2007). 17694074
- Hayakawa T. & Nakayama J. Physiological roles of class I HDAC complex and histone demethylase. J Biomed Biotechnol 2011, 129383 (2011). 21049000 PMC2964911
- de Ruijter A. J., van Gennip A. H., Caron H. N., Kemp S. & van Kuilenburg A. B. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370, 737– 49 (2003). 12429021 PMC1223209
- New M., Olzscha H. & La Thangue N. B. HDAC inhibitor-based therapies: can we interpret the code? Mol Oncol 6, 637– 56 (2012). 23141799 PMC5528347
- Huang W.. Coronin 2A mediates actin-dependent de-repression of inflammatory response genes. Nature 470, 414– 8 (2011). 21331046 PMC3464905
- Andrin C. & Hendzel M. J. F-actin-dependent insolubility of chromatin-modifying components. J Biol Chem 279, 25017– 23 (2004). 15082715
- Waltregny D.. Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility. FASEB J 19, 966– 8 (2005). 15772115
- Pollard T. D. & Cooper J. A. Actin, a central player in cell shape and movement. Science 326, 1208– 12 (2009). 19965462 PMC3677050
- de Lanerolle P. & Serebryannyy L. Nuclear actin and myosins: life without filaments. Nat Cell Biol 13, 1282– 8 (2011). 22048410
- Kapoor P., Chen M., Winkler D. D., Luger K. & Shen X. Evidence for monomeric actin function in INO80 chromatin remodeling. Nat Struct Mol Biol 20, 426– 32 (2013). 23524535 PMC3618487
- Tosi A.. Structure and subunit topology of the INO80 chromatin remodeler and its nucleosome complex. Cell 154, 1207– 19 (2013). 24034245
- Obrdlik A.. The histone acetyltransferase PCAF associates with actin and hnRNP U for RNA polymerase II transcription. Mol Cell Biol 28, 6342– 57 (2008). 18710935 PMC2577438
- Zhao K.. Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95, 625– 36 (1998). 9845365
- Szerlong H.. The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases. Nat Struct Mol Biol 15, 469– 76 (2008). 18408732 PMC2810487
- Qi T.. G-actin Participates in RNA Polymerase II-dependent Transcription Elongation by Recruiting Positive Transcription Elongation Factor b (P-TEFb). J Biol Chem 286, 15171– 81 (2011). 21378166 PMC3083233
- Fuchs M.. The p400 complex is an essential E1A transformation target. Cell 106, 297– 307 (2001). 11509179
- Ikura T.. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 102, 463– 73 (2000). 10966108
- Galarneau L.. Multiple links between the NuA4 histone acetyltransferase complex and epigenetic control of transcription. Mol Cell 5, 927– 37 (2000). 10911987
- Kapoor P. & Shen X. Mechanisms of nuclear actin in chromatin-remodeling complexes. Trends Cell Biol 24, 238– 46 (2014). 24246764 PMC3995414
- Posern G., Sotiropoulos A. & Treisman R. Mutant actins demonstrate a role for unpolymerized actin in control of transcription by serum response factor. Mol Biol Cell 13, 4167– 78 (2002). 12475943 PMC138624
- Murao S., Gemmell M. A., Callaham M. F., Anderson N. L. & Huberman E. Control of macrophage cell differentiation in human promyelocytic HL-60 leukemia cells by 1,25-dihydroxyvitamin D3 and phorbol-12-myristate-13-acetate. Cancer Res 43, 4989– 96 (1983). 6576856
- Wada T.. Expression levels of histone deacetylases determine the cell fate of hematopoietic progenitors. J Biol Chem 284, 30673– 83 (2009). 19736310 PMC2781621
- Yamagoe S.. Interaction of histone acetylases and deacetylases in vivo. Mol Cell Biol 23, 1025– 33 (2003). 12529406 PMC140702
- Xu Y. Z., Thuraisingam T., Morais D. A., Rola-Pleszczynski M. & Radzioch D. Nuclear translocation of beta-actin is involved in transcriptional regulation during macrophage differentiation of HL-60 cells. Mol Biol Cell 21, 811– 20 (2010). 20053683 PMC2828967
- Vaidya A. S.. Design, synthesis, modeling, biological evaluation and photoaffinity labeling studies of novel series of photoreactive benzamide probes for histone deacetylase 2. Bioorg Med Chem Lett 22, 5025– 30 (2012). 22771007 PMC3401313
- Abe A., Saeki K., Yasunaga T. & Wakabayashi T. Acetylation at the N-terminus of actin strengthens weak interaction between actin and myosin. Biochem Biophys Res Commun 268, 14– 9 (2000). 10652204
- Choudhary C.. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834– 40 (2009). 19608861
- Wulfkuhle J. D.. Domain analysis of supervillin, an F-actin bundling plasma membrane protein with functional nuclear localization signals. J Cell Sci 112 (Pt 13), 2125– 36 (1999). 10362542
- Szabo G. Jr., Damjanovich S., Sumegi J. & Klein G. Overall changes in chromatin sensitivity to DNase I during differentiation. Exp Cell Res 169, 158– 68 (1987). 3469102
- Weintraub H. & Groudine M. Chromosomal subunits in active genes have an altered conformation. Science 193, 848– 56 (1976). 948749
- Miller K. M.. Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol 17, 1144– 51 (2010). 20802485 PMC3018776
- Giannini G., Cabri W., Fattorusso C. & Rodriquez M. Histone deacetylase inhibitors in the treatment of cancer: overview and perspectives. Future Med Chem 4, 1439– 60 (2012). 22857533
- Hamada F. & Bienz M. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell 7, 677– 85 (2004). 15525529
- Moseley J. B.. Regulated binding of adenomatous polyposis coli protein to actin. J Biol Chem 282, 12661– 8 (2007). 17293347
- Lee M., Ji H., Furuta Y., Park J. I. & McCrea P. D. p120-catenin regulates REST and CoREST, and modulates mouse embryonic stem cell differentiation. J Cell Sci 127, 4037– 51 (2014). 25074806 PMC4163646
- Yap K. L.. NAC1 is an actin-binding protein that is essential for effective cytokinesis in cancer cells. Cancer Res 72, 4085– 96 (2012). 22761335 PMC3421062
- Korutla L., Degnan R., Wang P. & Mackler S. A. NAC1, a cocaine-regulated POZ/BTB protein interacts with CoREST. J Neurochem 101, 611– 8 (2007). 17254023
- Ito A.. The subcellular localization and activity of cortactin is regulated by acetylation and interaction with Keap1. Sci Signal 8, ra 120 (2015). 26602019
- Song E. H.. Acetylation of the RhoA GEF Net1A controls its subcellular localization and activity. J Cell Sci 128, 913– 22 (2015). 25588829 PMC4342578
- di Bari M. G.. c-Abl acetylation by histone acetyltransferases regulates its nuclear-cytoplasmic localization. EMBO Rep 7, 727– 33 (2006). 16648821 PMC1500821
- Fujita Y.. Zyxin is a novel interacting partner for SIRT1. BMC Cell Biol 10, 6 (2009). 19173742 PMC2642761
- Kim S. C.. Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23, 607– 18 (2006). 16916647
- Sadoul K., Wang J., Diagouraga B. & Khochbin S. The tale of protein lysine acetylation in the cytoplasm. J Biomed Biotechnol 2011, 970382 (2011). 21151618 PMC2997609
- Schubert H. L.. Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler. Proc Natl Acad Sci USA 110, 3345– 50 (2013). 23401505 PMC3587198
- Rando O. J., Zhao K., Janmey P. & Crabtree G. R. Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex. Proc Natl Acad Sci USA 99, 2824– 9 (2002). 11880634 PMC122432
- Miyamoto K., Pasque V., Jullien J. & Gurdon J. B. Nuclear actin polymerization is required for transcriptional reprogramming of Oct4 by oocytes. Genes Dev 25, 946– 58 (2011). 21536734 PMC3084028
- Vartiainen M. K., Guettler S., Larijani B. & Treisman R. Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL. Science 316, 1749– 52 (2007). 17588931
- Baarlink C., Wang H. & Grosse R. Nuclear actin network assembly by formins regulates the SRF coactivator MAL. Science 340, 864– 7 (2013). 23558171
- Belin B. J., Cimini B. A., Blackburn E. H. & Mullins R. D. Visualization of actin filaments and monomers in somatic cell nuclei. Mol Biol Cell 24, 982– 94 (2013). 23447706 PMC3608506
Cited by
Sorted by citations
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Serebryannyy, L. A., Cruz, C. M., & de Lanerolle, P.
- Affiliations
- University of Illinois Chicago (US)
- Venue
- Scientific Reports
- Published
- 2016-06-27
- Volume
- 6
- Issue
- 1
- Pages
- 28460-28460
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4921920
- OpenAlex
- W2460292857
- Cited by
- 67
- References
- 4
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 11 · 2023: 4 · 2022: 3 · 2021: 9 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 3
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association (13PRE17050060)
- Chicago Community Trust
- Northwestern University
- Chicago Biomedical Consortium
- National Institutes of Health
- University of Illinois at Urbana-Champaign
- National Cancer Institute (U54CA143869)
- National Institute of General Medical Sciences (R01GM080587)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- nuclear actin, HDAC1, HDAC2, class I HDACs, histone acetylation, actin polymerization, protein-protein interaction, chromatin remodeling, transcriptional repression
- MeSH terms
- Actins, Animals, Cell Nucleus, Chlorocebus aethiops, HeLa Cells, Humans, Actin Cytoskeleton, Microscopy, Fluorescence, COS Cells, Immunoprecipitation, Histone Deacetylase 1, Histone Deacetylase 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
