Gene Symbol: Sin3a
Description: transcriptional regulator, SIN3A (yeast)
Alias: AW553200, Sin3, mKIAA4126, mSin3A, paired amphipathic helix protein Sin3a, histone deacetylase complex subunit Sin3a, transcriptional corepressor Sin3a, transcriptional regulator, SIN3 yeast homolog A
Species: mouse
Products:     Sin3a

Top Publications

  1. Yang S, Vickers E, Brehm A, Kouzarides T, Sharrocks A. Temporal recruitment of the mSin3A-histone deacetylase corepressor complex to the ETS domain transcription factor Elk-1. Mol Cell Biol. 2001;21:2802-14 pubmed
    ..activation domain, Elk-1 contains an N-terminal transcriptional repression domain that can recruit the mSin3A-histone deacetylase 1 corepressor complex...
  2. David G, Dannenberg J, Simpson N, Finnerty P, Miao L, Turner G, et al. Haploinsufficiency of the mSds3 chromatin regulator promotes chromosomal instability and cancer only upon complete neutralization of p53. Oncogene. 2006;25:7354-60 pubmed
    ..In contrast, mSin3A nullizygous cells show normal chromosome dynamics and cytogenetic profiles...
  3. Wilkinson D, Tsai W, Schumacher M, Barton M. Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression. Mol Cell Biol. 2008;28:1988-98 pubmed publisher
    ..We find that p53 anchors activated Smads and the corepressor mSin3A to the AFP distal promoter...
  4. Lin T, Chao C, Saito S, Mazur S, Murphy M, Appella E, et al. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol. 2005;7:165-71 pubmed
    ..Nanog expression in p53(S315A) ESCs during differentiation is due to an impaired recruitment of the co-repressor mSin3a to the Nanog promoter...
  5. Alland L, David G, Shen Li H, Potes J, Muhle R, Lee H, et al. Identification of mammalian Sds3 as an integral component of the Sin3/histone deacetylase corepressor complex. Mol Cell Biol. 2002;22:2743-50 pubmed
    ..The mammalian corepressors mSin3A and mSin3B have been shown to play a key role in this process by tethering HDACs 1 and 2 to promoter-bound ..
  6. Hurlin P, Queva C, Koskinen P, Steingrimsson E, Ayer D, Copeland N, et al. Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J. 1995;14:5646-59 pubmed
  7. Dannenberg J, David G, Zhong S, van der Torre J, Wong W, Depinho R. mSin3A corepressor regulates diverse transcriptional networks governing normal and neoplastic growth and survival. Genes Dev. 2005;19:1581-95 pubmed
    b>mSin3A is a core component of a large multiprotein corepressor complex with associated histone deacetylase (HDAC) enzymatic activity...
  8. Grimes J, Nielsen S, Battaglioli E, Miska E, Speh J, Berry D, et al. The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. J Biol Chem. 2000;275:9461-7 pubmed
    ..and Mandel, G. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 9873-9878). Here we show that the co-repressor mSin3A also interacts with REST...
  9. Moehren U, Dressel U, Reeb C, Väisänen S, Dunlop T, Carlberg C, et al. The highly conserved region of the co-repressor Sin3A functionally interacts with the co-repressor Alien. Nucleic Acids Res. 2004;32:2995-3004 pubmed
    ..The paired amphipathic helices of Sin3A were identified and studied as protein-protein interacting domains...

More Information


  1. Cowley S, Iritani B, Mendrysa S, Xu T, Cheng P, Yada J, et al. The mSin3A chromatin-modifying complex is essential for embryogenesis and T-cell development. Mol Cell Biol. 2005;25:6990-7004 pubmed
    The corepressor mSin3A is the core component of a chromatin-modifying complex that is recruited by multiple gene-specific transcriptional repressors...
  2. Meroni G, Cairo S, Merla G, Messali S, Brent R, Ballabio A, et al. Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway?. Oncogene. 2000;19:3266-77 pubmed
    ..The possible role of Mlx in an emerging regulatory pathway and acting parallel to the Max driven network is discussed. ..
  3. van Oevelen C, Wang J, Asp P, Yan Q, Kaelin W, Kluger Y, et al. A role for mammalian Sin3 in permanent gene silencing. Mol Cell. 2008;32:359-70 pubmed publisher
    The multisubunit Sin3 corepressor complex regulates gene transcription through deacetylation of nucleosomes. However, the full range of Sin3 activities and targets is not well understood...
  4. Rao G, Alland L, Guida P, Schreiber Agus N, Chen K, Chin L, et al. Mouse Sin3A interacts with and can functionally substitute for the amino-terminal repression of the Myc antagonist Mxi1. Oncogene. 1996;12:1165-72 pubmed
    ..Here, we sought to characterize more fully the physical properties of the second homologue, mSin3A and to determine whether the recruitment of mSin3A by Mxi1 is indeed required for anti-Myc activity...
  5. Heinzel T, Lavinsky R, Mullen T, Soderstrom M, Laherty C, Torchia J, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature. 1997;387:43-8 pubmed
  6. Kaczynski J, Zhang J, Ellenrieder V, Conley A, Duenes T, Kester H, et al. The Sp1-like protein BTEB3 inhibits transcription via the basic transcription element box by interacting with mSin3A and HDAC-1 co-repressors and competing with Sp1. J Biol Chem. 2001;276:36749-56 pubmed
    ..Immunoprecipitation assays reveal that BTEB3 interacts with the co-repressor mSin3A and the histone deacetylase protein HDAC-1...
  7. Williams K, Christensen J, Pedersen M, Johansen J, Cloos P, Rappsilber J, et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature. 2011;473:343-8 pubmed publisher
    ..Furthermore, TET1 associates and colocalizes with the SIN3A co-repressor complex...
  8. Nascimento E, Cox C, MacArthur S, Hussain S, Trotter M, Blanco S, et al. The opposing transcriptional functions of Sin3a and c-Myc are required to maintain tissue homeostasis. Nat Cell Biol. 2011;13:1395-405 pubmed publisher
    ..Binding of c-Myc can simultaneously recruit (Klf4, Ovol-1) and displace (Cebpa, Mxi1 and Sin3a) specific sets of differentiation-specific transcriptional regulators to epidermal differentiation complex genes...
  9. Laherty C, Billin A, Lavinsky R, Yochum G, Bush A, Sun J, et al. SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors. Mol Cell. 1998;2:33-42 pubmed
  10. Dovey O, Foster C, Cowley S. Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci U S A. 2010;107:8242-7 pubmed publisher
    ..Deletion of HDAC1, but not HDAC2, causes a significant reduction in the HDAC activity of Sin3A, NuRD, and CoREST corepressor complexes. This reduced corepressor activity results in a specific 1...
  11. Baltus G, Kowalski M, Tutter A, Kadam S. A positive regulatory role for the mSin3A-HDAC complex in pluripotency through Nanog and Sox2. J Biol Chem. 2009;284:6998-7006 pubmed publisher
    ..has identified their interaction with multiple transcriptional repression complexes, including members of the mSin3A-HDAC complex, suggesting that these factors could be involved in the regulation of Oct4/Nanog function...
  12. Trumpp A, Refaeli Y, Oskarsson T, Gasser S, Murphy M, Martin G, et al. c-Myc regulates mammalian body size by controlling cell number but not cell size. Nature. 2001;414:768-73 pubmed
    ..We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size. ..
  13. Brown M, Sims R, Gottlieb P, Tucker P. Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex. Mol Cancer. 2006;5:26 pubmed
    ..Smyd2 associates specifically with the Sin3A histone deacetylase complex, which was recently linked to H3K36 methylation within the coding regions of active ..
  14. Ma P, De Waal E, Weaver J, Bartolomei M, Schultz R. A DNMT3A2-HDAC2 Complex Is Essential for Genomic Imprinting and Genome Integrity in Mouse Oocytes. Cell Rep. 2015;13:1552-60 pubmed publisher
    ..Partial loss of nuclear DNMT3A2 and HDAC2 occurs in Sin3a(-/-) oocytes, which exhibit decreased DNA methylation of imprinting control regions for Igf2r and Srnpn, but not ..
  15. Craig J, Earle E, Canham P, Wong L, Anderson M, Choo K. Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns. Hum Mol Genet. 2003;12:3109-21 pubmed
    ..centromeres, a neocentromere, and the active centromere of a dicentric chromosome, with six of these proteins (Sin3A, PCAF, MYST, MBD2, ORC2, P300/CBP) being demonstrated at mammalian centromeres for the first time...
  16. Sengupta S, Chattopadhyay R, Mantha A, Mitra S, Bhakat K. Regulation of mouse-renin gene by apurinic/apyrimidinic-endonuclease 1 (APE1/Ref-1) via recruitment of histone deacetylase 1 corepressor complex. J Hypertens. 2012;30:917-25 pubmed publisher
    ..This study uncovers APE1's function as a novel negative regulator of renin expression, and thereby in blood pressure maintenance. ..
  17. Gallagher S, Kofman A, Huszar J, Dannenberg J, Depinho R, Braun R, et al. Distinct requirements for Sin3a in perinatal male gonocytes and differentiating spermatogonia. Dev Biol. 2013;373:83-94 pubmed publisher
    Chromatin modifier Swi-independent 3a (SIN3A), together with associated histone deacetylases, influences gene expression during development and differentiation through a variety of transcription factors in a cell-specific manner...
  18. Dressel U, Thormeyer D, Altincicek B, Paululat A, Eggert M, Schneider S, et al. Alien, a highly conserved protein with characteristics of a corepressor for members of the nuclear hormone receptor superfamily. Mol Cell Biol. 1999;19:3383-94 pubmed
    ..These properties, taken together, show that Alien has the characteristics of a corepressor. Thus, Alien represents a member of a novel class of corepressors specific for selected members of the nuclear hormone receptor superfamily. ..
  19. Jimenez R, Melo E, Davydenko O, Ma J, Mainigi M, Franke V, et al. Maternal SIN3A regulates reprogramming of gene expression during mouse preimplantation development. Biol Reprod. 2015;93:89 pubmed publisher
    ..Because SIN3A is an HDAC1/2-containing complex, we investigated whether it is involved in reprogramming gene expression during ..
  20. Goffin D, Allen M, Zhang L, Amorim M, Wang I, Reyes A, et al. Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Nat Neurosci. 2011;15:274-83 pubmed publisher
  21. Ellenrieder V, Buck A, Harth A, Jungert K, Buchholz M, Adler G, et al. KLF11 mediates a critical mechanism in TGF-beta signaling that is inactivated by Erk-MAPK in pancreatic cancer cells. Gastroenterology. 2004;127:607-20 pubmed
    ..real-time polymerase chain reaction, and coimmunoprecipitation studies were performed to study KLF11-induced and mSin3A corepressor-mediated repression of Smad7...
  22. Spronk C, Tessari M, Kaan A, Jansen J, Vermeulen M, Stunnenberg H, et al. The Mad1-Sin3B interaction involves a novel helical fold. Nat Struct Biol. 2000;7:1100-4 pubmed
    b>Sin3A or Sin3B are components of a corepressor complex that mediates repression by transcription factors such as the helix-loop-helix proteins Mad and Mxi...
  23. Iso T, Sartorelli V, Poizat C, Iezzi S, Wu H, Chung G, et al. HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling. Mol Cell Biol. 2001;21:6080-9 pubmed
    ..Thus, Notch signaling relies on cooperation between HES and HERP, two transcriptional repressors with distinctive repression mechanisms which, either as homo- or as heterodimers, regulate target gene expression. ..
  24. Li Z, David G, Hung K, Depinho R, Fu A, Ip N. Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of transcription. J Biol Chem. 2004;279:54438-44 pubmed
  25. Solaimani P, Wang F, Hankinson O. SIN3A, generally regarded as a transcriptional repressor, is required for induction of gene transcription by the aryl hydrocarbon receptor. J Biol Chem. 2014;289:33655-62 pubmed publisher
    ..described an RNAi high throughput screening performed in the Hepa-1 mouse hepatoma cell line, which revealed that SIN3A is necessary for the induction of CYP1A1-dependent ethoxyresorufin-o-deethylase (EROD) enzymatic activity by TCDD...
  26. Yao C, Carraro G, Konda B, Guan X, Mizuno T, Chiba N, et al. Sin3a regulates epithelial progenitor cell fate during lung development. Development. 2017;144:2618-2628 pubmed publisher
    ..Here, we demonstrate that the co-repressor protein Sin3a is crucial for lung endoderm development...
  27. Zhou Y, Santoro R, Grummt I. The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription. EMBO J. 2002;21:4632-40 pubmed
    ..The results suggest that NoRC silences the rDNA locus by targeting the SIN3 corepressor complex to the rDNA promoter, thereby establishing a repressed chromatin structure.
  28. Yang L, Mei Q, Zielinska Kwiatkowska A, Matsui Y, Blackburn M, Benedetti D, et al. An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B. Biochem J. 2003;369:651-7 pubmed
    ..with histone deacetylase 1 (HDAC1) and HDAC2, and that ESET also interacts with the transcription co-repressors mSin3A and mSin3B...
  29. Petrie K, Guidez F, Howell L, Healy L, Waxman S, Greaves M, et al. The histone deacetylase 9 gene encodes multiple protein isoforms. J Biol Chem. 2003;278:16059-72 pubmed
    ..These results suggest that HDAC9 plays a role in hematopoiesis; its deregulated expression may be associated with some human cancers. ..
  30. Langlet F, Haeusler R, Lindén D, Ericson E, Norris T, Johansson A, et al. Selective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic Glucose Handling. Cell. 2017;171:824-835.e18 pubmed publisher
    ..Here, we report that SIN3A is the insulin-sensitive FOXO1 corepressor of glucokinase...
  31. Saunders A, Huang X, Fidalgo M, Reimer M, Faiola F, Ding J, et al. The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency. Cell Rep. 2017;18:1713-1726 pubmed publisher
    Although SIN3A is required for the survival of early embryos and embryonic stem cells (ESCs), the role of SIN3A in the maintenance and establishment of pluripotency remains unclear...
  32. Winter S, Lukes L, Walker R, Welch D, Hunter K. Allelic variation and differential expression of the mSIN3A histone deacetylase complex gene Arid4b promote mammary tumor growth and metastasis. PLoS Genet. 2012;8:e1002735 pubmed publisher
    ..BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying ..
  33. Naruse Y, Aoki T, Kojima T, Mori N. Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes. Proc Natl Acad Sci U S A. 1999;96:13691-6 pubmed
  34. Amann J, Chyla B, Ellis T, Martinez A, Moore A, Franklin J, et al. Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine. Mol Cell Biol. 2005;25:9576-85 pubmed
    ..We demonstrate that Mtgr1 associates with mSin3A, N-CoR, and histone deacetylase 3 and that when tethered to DNA, Mtgr1 represses transcription, suggesting that ..
  35. Hu Z, Gu X, Baraoidan K, Ibanez V, Sharma A, Kadkol S, et al. RUNX1 regulates corepressor interactions of PU.1. Blood. 2011;117:6498-508 pubmed publisher decreased histone acetylation at the Mcsfr and Gmcsfr promoters, and increased endogenous corepressor (Eto2, Sin3A, and Hdac2) coimmunoprecipitation with Pu.1...
  36. O Shaughnessy Kirwan A, Signolet J, Costello I, Gharbi S, Hendrich B. Constraint of gene expression by the chromatin remodelling protein CHD4 facilitates lineage specification. Development. 2015;142:2586-97 pubmed publisher
    ..This provides novel insight into both how lineage decisions are made in mammalian cells, and how a chromatin remodelling protein functions to facilitate lineage commitment. ..
  37. Steffan J, Kazantsev A, Spasic Boskovic O, Greenwald M, Zhu Y, Gohler H, et al. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc Natl Acad Sci U S A. 2000;97:6763-8 pubmed
    ..httex1p was also found to interact in vitro with CREB-binding protein (CBP) and mSin3a, and CBP to localize to neuronal intranuclear inclusions in a transgenic mouse model of HD...
  38. Gómez del Arco P, Koipally J, Georgopoulos K. Ikaros SUMOylation: switching out of repression. Mol Cell Biol. 2005;25:2688-97 pubmed
    ..These studies reveal a new dynamic way by which Ikaros-mediated gene repression is controlled by SUMOylation. ..
  39. Streubel G, Fitzpatrick D, Oliviero G, Scelfo A, Moran B, Das S, et al. Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal. EMBO J. 2017;36:2216-2232 pubmed publisher
    b>Sin3a is the central scaffold protein of the prototypical Hdac1/2 chromatin repressor complex, crucially required during early embryonic development for the growth of pluripotent cells of the inner cell mass...
  40. Bach I, Rodriguez Esteban C, Carriere C, Bhushan A, Krones A, Rose D, et al. RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nat Genet. 1999;22:394-9 pubmed
    ..for RING finger LIM domain-binding protein), which acts as a negative co-regulator via the recruitment of the Sin3A/histone deacetylase corepressor complex...
  41. Shi X, Seldin D, Garry D. Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors. Biochem J. 2012;446:349-57 pubmed publisher
    ..we report the identification of Sds3 (suppressor of defective silencing 3) as an adaptor protein that recruits the Sin3 [SWI (switch)-independent 3]-HDAC (histone deacetylase) repression complex and binds Foxk1...
  42. Lyst M, Ekiert R, Ebert D, Merusi C, Nowak J, Selfridge J, et al. Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor. Nat Neurosci. 2013;16:898-902 pubmed publisher
    ..Our data are compatible with the hypothesis that brain dysfunction in RTT is caused by a loss of the MeCP2 'bridge' between the NCoR/SMRT co-repressors and chromatin. ..
  43. Doetzlhofer A, Rotheneder H, Lagger G, Koranda M, Kurtev V, Brosch G, et al. Histone deacetylase 1 can repress transcription by binding to Sp1. Mol Cell Biol. 1999;19:5504-11 pubmed
    ..Our results indicate that one component of Sp1-dependent gene regulation involves competition between the transcriptional repressor HDAC1 and the transactivating factor E2F1. ..
  44. Seki M, Masaki H, Arauchi T, Nakauchi H, Sugano S, Suzuki Y. A comparison of the rest complex binding patterns in embryonic stem cells and epiblast stem cells. PLoS ONE. 2014;9:e95374 pubmed publisher
    We detected and characterized the binding sites of the representative Rest complex components Rest, Sin3A, and Lsd1. We compared their binding patterns in mouse embryonic stem (ES) cells and epiblast stem (EpiS) cells...
  45. Cox E, Marsh S. Exercise and diabetes have opposite effects on the assembly and O-GlcNAc modification of the mSin3A/HDAC1/2 complex in the heart. Cardiovasc Diabetol. 2013;12:101 pubmed publisher
    Exercise causes physiological cardiac hypertrophy and benefits the diabetic heart. Mammalian switch-independent 3A (mSin3A) and histone deacetylases (HDACs) 1 and 2 regulate hypertrophic genes through associations with the DNA binding ..
  46. Lui W, Wong E, Guan Y, Lee W. Dual transcriptional control of claudin-11 via an overlapping GATA/NF-Y motif: positive regulation through the interaction of GATA, NF-YA, and CREB and negative regulation through the interaction of Smad, HDAC1, and mSin3A. J Cell Physiol. 2007;211:638-48 pubmed
    ..repression which required the recruitment and physical interactions of histone deacetylase 1 and its co-repressor, mSin3A with Smad proteins, was abolished by treatment with Trichostatin A, thus suggesting the involvement of histone ..
  47. Ayer D, Lawrence Q, Eisenman R. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell. 1995;80:767-76 pubmed
    ..b>mSin3A and mSin3B bind specifically to Mad and the related protein Mxi1...
  48. Waga K, Nakamura Y, Maki K, Arai H, Yamagata T, Sasaki K, et al. Leukemia-related transcription factor TEL accelerates differentiation of Friend erythroleukemia cells. Oncogene. 2003;22:59-68 pubmed
    ..TEL bound to a corepressor mSin3A through the helix-loop-helix domain...
  49. Lutz M, Burke L, Barreto G, Goeman F, Greb H, Arnold R, et al. Transcriptional repression by the insulator protein CTCF involves histone deacetylases. Nucleic Acids Res. 2000;28:1707-13 pubmed
    ..the zinc-finger cluster, silences transcription in all cell types tested and binds directly to the co-repressor SIN3A. Two distinct regions of SIN3A, the PAH3 domain and the extreme C-terminal region, bind independently to this zinc-..
  50. Pellegrino J, Castrillon D, David G. Chromatin associated Sin3A is essential for male germ cell lineage in the mouse. Dev Biol. 2012;369:349-55 pubmed publisher
    ..In this study, we investigate the contribution of chromatin associated Sin3A in mouse germ cell lineage development...
  51. Popov N, Wahlström T, Hurlin P, Henriksson M. Mnt transcriptional repressor is functionally regulated during cell cycle progression. Oncogene. 2005;24:8326-37 pubmed
    ..Our data suggest a model in which phosphorylation of Mnt at cell cycle entry results in disruption of Mnt-mSin3-HDAC1 interaction, which allows induction of Myc target genes by release of Mnt-mediated transcriptional repression. ..
  52. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 2003;302:890-3 pubmed
    ..Moreover, increased Bdnf transcription involves dissociation of the MeCP2-histone deacetylase-mSin3A repression complex from its promoter...
  53. Cheng S, Bishop J. Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex. Proc Natl Acad Sci U S A. 2002;99:5442-7 pubmed
    ..These results provide biochemical evidence that Su(fu) directly participates in modulating the transcriptional activity of Gli. ..