Gene Symbol: Zac1
Description: pleiomorphic adenoma gene-like 1
Alias: Lot1, Zac1, zinc finger protein PLAGL1, zinc finger protein regulator of apoptosis and cell cycle arrest
Species: mouse
Products:     Zac1

Top Publications

  1. Varrault A, Gueydan C, Delalbre A, Bellmann A, Houssami S, Aknin C, et al. Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev Cell. 2006;11:711-22 pubmed
    ..We show that inactivation of the maternally repressed Zac1 transcription factor results in intrauterine growth restriction, altered bone formation, and neonatal lethality...
  2. Valente T, Junyent F, Auladell C. Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm during embryogenesis: differential phenotype of the Zac1-expressing cells during development. Dev Dyn. 2005;233:667-79 pubmed
    b>Zac1, a new zinc-finger protein that regulates both apoptosis and cell cycle arrest, is abundantly expressed in many neuroepithelia during early brain development...
  3. Ma L, Cantrup R, Varrault A, Colak D, Klenin N, Gotz M, et al. Zac1 functions through TGFbetaII to negatively regulate cell number in the developing retina. Neural Dev. 2007;2:11 pubmed
    ..Here we report a similar role for two tumor suppressor genes, the Zac1 zinc finger transcription factor and that encoding the cytokine TGFbetaII, in the developing retina...
  4. Piras G, El Kharroubi A, Kozlov S, Escalante Alcalde D, Hernandez L, Copeland N, et al. Zac1 (Lot1), a potential tumor suppressor gene, and the gene for epsilon-sarcoglycan are maternally imprinted genes: identification by a subtractive screen of novel uniparental fibroblast lines. Mol Cell Biol. 2000;20:3308-15 pubmed
    ..Here we show that the epsilon-sarcoglycan gene (Sgce) and Zac1 (Lot1) are both paternally expressed imprinted genes...
  5. Arima T, Drewell R, Oshimura M, Wake N, Surani M. A novel imprinted gene, HYMAI, is located within an imprinted domain on human chromosome 6 containing ZAC. Genomics. 2000;67:248-55 pubmed
    ..A previously characterized imprinted gene, ZAC/LOT1, is located 70 kb downstream of HYMAI and is also expressed only from the paternal allele...
  6. Valente T, Auladell C. Expression pattern of Zac1 mouse gene, a new zinc-finger protein that regulates apoptosis and cellular cycle arrest, in both adult brain and along development. Mech Dev. 2001;108:207-11 pubmed
    Using in situ hybridization, we analyzed the expression pattern of the Zac1 gene in mouse brain during the embryonic and postnatal development...
  7. Smith R, Arnaud P, Konfortova G, Dean W, Beechey C, Kelsey G. The mouse Zac1 locus: basis for imprinting and comparison with human ZAC. Gene. 2002;292:101-12 pubmed
    ..10 in a screen for imprinted genes. The homologous human gene ZAC (also known as LOT1 and PLAGLI) is a candidate gene for transient neonatal diabetes (TNDM), an imprinted disorder associated with ..
  8. Alam S, Zinyk D, Ma L, Schuurmans C. Members of the Plag gene family are expressed in complementary and overlapping regions in the developing murine nervous system. Dev Dyn. 2005;234:772-82 pubmed
    ..gene (Plag) family, which encode zinc finger transcription factors previously characterized as tumor suppressors (Zac1) or oncogenes (Plag1, Plag-l2)...
  9. Huang S, Stallcup M. Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors. Mol Cell Biol. 2000;20:1855-67 pubmed
    ..the C-terminal activation domain of the nuclear receptor coactivator GRIP1, we identified a new variant of mouse Zac1 which we call mZac1b...

More Information


  1. Ma L, Hocking J, Hehr C, Schuurmans C, McFarlane S. Zac1 promotes a Müller glial cell fate and interferes with retinal ganglion cell differentiation in Xenopus retina. Dev Dyn. 2007;236:192-202 pubmed
    ..Here we investigated the role of Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, in retinal development...
  2. Ma D, Shield J, Dean W, Leclerc I, Knauf C, Burcelin R R, et al. Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM. J Clin Invest. 2004;114:339-48 pubmed
    ..Expression of human ZAC and HYMAI in these transgenic mice thus recapitulates key features of TNDM and implicates impaired development of the endocrine pancreas and beta cell function in disease pathogenesis. ..
  3. Spengler D, Villalba M, Hoffmann A, Pantaloni C, Houssami S, Bockaert J, et al. Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain. EMBO J. 1997;16:2814-25 pubmed
    ..cloning of a novel zinc finger protein which regulates apoptosis and cell cycle arrest and was accordingly named Zac1. In vitro Zac1 inhibited proliferation of tumor cells, as evidenced by measuring colony formation, growth rate and ..
  4. Tsuda T, Markova D, Wang H, Evangelisti L, Pan T, Chu M. Zinc finger protein Zac1 is expressed in chondrogenic sites of the mouse. Dev Dyn. 2004;229:340-8 pubmed
    b>Zac1 is a zinc finger transcription factor that elicits antiproliferative activity and is a potential tumor suppressor gene...
  5. Arima T, Drewell R, Arney K, Inoue J, Makita Y, Hata A, et al. A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. Hum Mol Genet. 2001;10:1475-83 pubmed
    ..We propose that this ICR regulates expression of imprinted genes within the domain; epigenetic or genetic mutations of this region probably result in TNDM, possibly by affecting expression of ZAC in the pancreas and/or the pituitary. ..
  6. Lui J, Finkielstain G, Barnes K, Baron J. An imprinted gene network that controls mammalian somatic growth is down-regulated during postnatal growth deceleration in multiple organs. Am J Physiol Regul Integr Comp Physiol. 2008;295:R189-96 pubmed publisher
  7. Arima T, Kamikihara T, Hayashida T, Kato K, Inoue T, Shirayoshi Y, et al. ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome. Nucleic Acids Res. 2005;33:2650-60 pubmed
    ..Patients with these diseases share many characteristics. Here we show that mouse Zac1 and p57Kip2 have a strikingly similar expression pattern...
  8. Czubryt M, Lamoureux L, Ramjiawan A, Abrenica B, Jangamreddy J, Swan K. Regulation of cardiomyocyte Glut4 expression by ZAC1. J Biol Chem. 2010;285:16942-50 pubmed publisher
    The transcription factor ZAC1 is expressed in a variety of tissues including the developing heart, but its physiological role is unclear...
  9. Schmidt Edelkraut U, Daniel G, Hoffmann A, Spengler D. Zac1 regulates cell cycle arrest in neuronal progenitors via Tcf4. Mol Cell Biol. 2014;34:1020-30 pubmed publisher
    ..Here, we identified the bHLH factor gene Tcf4 as a direct target gene of Zac1/Plagl1, a maternally imprinted transcriptional regulator, during early neurogenesis...
  10. Hoffmann A, Spengler D. A new coactivator function for Zac1's C2H2 zinc finger DNA-binding domain in selectively controlling PCAF activity. Mol Cell Biol. 2008;28:6078-93 pubmed publisher
    ..The C(2)H(2) zinc finger protein Zac1, with an established role in canonical DNA binding, also acts as a coactivator...
  11. Wang W, Liu S, Huang S, Lin W, Chen S, Chang Y. Zac1 functional interactions mediate AP-1 transcriptional activity. Biochim Biophys Acta. 2011;1813:2050-60 pubmed publisher
    A zinc-finger protein which regulates apoptosis and cell cycle arrest 1 (Zac1) is a novel seven-zinc-finger protein that can bind a specific GC-rich DNA element and has intrinsic transactivation activity; therefore, its role as a ..
  12. Gabory A, Ripoche M, Le Digarcher A, Watrin F, Ziyyat A, Forné T, et al. H19 acts as a trans regulator of the imprinted gene network controlling growth in mice. Development. 2009;136:3413-21 pubmed publisher
    ..Our results also bring further experimental evidence for the existence of the IGN and open new perspectives in the comprehension of the role of genomic imprinting in embryonic growth and in human imprinting pathologies. ..
  13. Iglesias Platas I, Martin Trujillo A, Cirillo D, Court F, Guillaumet Adkins A, Camprubí C, et al. Characterization of novel paternal ncRNAs at the Plagl1 locus, including Hymai, predicted to interact with regulators of active chromatin. PLoS ONE. 2012;7:e38907 pubmed publisher
    ..The two ncRNAs could therefore help to protect the paternal allele from DNA methylation by attracting Trithorax proteins that mediate H3 lysine-4 methylation. ..
  14. Varrault A, Dantec C, Le Digarcher A, Chotard L, Bilanges B, Parrinello H, et al. Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network. Nucleic Acids Res. 2017;45:10466-10480 pubmed publisher
    PLAGL1/ZAC1 undergoes parental genomic imprinting, is paternally expressed, and is a member of the imprinted gene network (IGN)...
  15. Arima T, Wake N. Establishment of the primary imprint of the HYMAI/PLAGL1 imprint control region during oogenesis. Cytogenet Genome Res. 2006;113:247-52 pubmed
    ..This domain contains two paternally expressed genes, the zinc finger protein gene PLAGL1 (ZAC/LOT1) and an untranslated mRNAcalled HYMAI...
  16. Abdollahi A, Bao R, Hamilton T. LOT1 is a growth suppressor gene down-regulated by the epidermal growth factor receptor ligands and encodes a nuclear zinc-finger protein. Oncogene. 1999;18:6477-87 pubmed
    ..Interestingly, the LOT1 gene localized at band q25 of human chromosome 6 which is a frequent site for LOH in many solid tumors including ..
  17. Chotalia M, Smallwood S, Ruf N, Dawson C, Lucifero D, Frontera M, et al. Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev. 2009;23:105-17 pubmed publisher
  18. Pagotto U, Arzberger T, Ciani E, Lezoualc H F, Pilon C, Journot L, et al. Inhibition of Zac1, a new gene differentially expressed in the anterior pituitary, increases cell proliferation. Endocrinology. 1999;140:987-96 pubmed
    b>Zac1 is a new zinc finger protein that concomitantly controls apoptosis and cell cycle arrest through separate pathways. The mouse Zac1 gene is mainly expressed in the pituitary gland and in different brain areas...
  19. Billington C, Ng B, Forsman C, Schmidt B, Bagchi A, Symer D, et al. The molecular and cellular basis of variable craniofacial phenotypes and their genetic rescue in Twisted gastrulation mutant mice. Dev Biol. 2011;355:21-31 pubmed publisher
    ..We postulate that variable responses to stress may contribute to variable craniofacial phenotypes by triggering differential expression of genes and variable cellular apoptosis. ..
  20. Williams J, Kondo N, Okabe T, Takeshita N, Pilchak D, Koyama E, et al. Retinoic acid receptors are required for skeletal growth, matrix homeostasis and growth plate function in postnatal mouse. Dev Biol. 2009;328:315-27 pubmed publisher chondrocytes under retinoid-free culture conditions; production is further boosted by co-repressor Zac1 or pharmacologic agents that enhance RAR repressor function; and RAR/Zac1 function on aggrecan expression may ..
  21. Fan T, Hagan J, Kozlov S, Stewart C, Muegge K. Lsh controls silencing of the imprinted Cdkn1c gene. Development. 2005;132:635-44 pubmed
    ..Cdkn1c gene (also known as p57(Kip2)) but does not interfere with maintenance of imprints at the H19, Igf2, Igf2r, Zac1 and Meg9 genes...
  22. Rajan S, Chu Pham Dang H, Djambazian H, Zuzan H, Fedyshyn Y, Ketela T, et al. Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation. Physiol Genomics. 2012;44:183-97 pubmed publisher
  23. Shu G, Tang Y, Zhou Y, Wang C, Song J. Zac1 is a histone acetylation-regulated NF-?B suppressor that mediates histone deacetylase inhibitor-induced apoptosis. Cell Death Differ. 2011;18:1825-35 pubmed publisher
    ..Here we show that increased expression of zinc-finger protein regulator of apoptosis and cell-cycle arrest (Zac1) is implicated in HDAC inhibitor-induced apoptosis in F9 and P19 EC cells...
  24. Valente T, Domínguez M, Bellmann A, Journot L, Ferrer I, Auladell C. Zac1 is up-regulated in neural cells of the limbic system of mouse brain following seizures that provoke strong cell activation. Neuroscience. 2004;128:323-36 pubmed
    b>Zac1, a new zinc-finger protein that regulates both apoptosis and cell cycle arrest, is abundantly expressed in many proliferative/differentiation areas during brain development...
  25. Anderson A, Helmering J, Juan T, Li C, McCormick J, Graham M, et al. Pancreatic islet expression profiling in diabetes-prone C57BLKS/J mice reveals transcriptional differences contributed by DBA loci, including Plagl1 and Nnt. Pathogenetics. 2009;2:1 pubmed publisher
    ..This study describes physiological differences between BLKS and B6 mice, and provides evidence for a causative role of the DBA genome in beta-cell dysfunction in BLKS mice. ..
  26. Yuasa S, Onizuka T, Shimoji K, Ohno Y, Kageyama T, Yoon S, et al. Zac1 is an essential transcription factor for cardiac morphogenesis. Circ Res. 2010;106:1083-91 pubmed publisher
    ..To isolate novel cardiac transcription factors, we performed gene chip analysis and found that Zac1, a zinc finger-type transcription factor, was strongly expressed in the developing heart...
  27. Liang Y, Yuan W, Zhu W, Zhu J, Lin Q, Zou X, et al. Macrophage migration inhibitory factor promotes expression of GLUT4 glucose transporter through MEF2 and Zac1 in cardiomyocytes. Metabolism. 2015;64:1682-93 pubmed publisher
    ..Expressions of transcription factor MEF2A, -2C, -2D and Zac1 were significantly up-regulated in MIF-treated neonatal mouse ventricular cardiomyocytes (NMVCs), and markedly ..
  28. Theodoropoulou M, Stalla G, Spengler D. ZAC1 target genes and pituitary tumorigenesis. Mol Cell Endocrinol. 2010;326:60-5 pubmed publisher
    The zinc-finger protein Zac1 has a role as transcription factor and coregulator and plays an important role in pituitary development, maturation and tumorigenesis. Zac1 target genes control cell proliferation and hormone synthesis...
  29. Du X, Rousseau M, Ounissi Benkalha H, Marchand L, Jetha A, Paraskevas S, et al. Differential expression pattern of ZAC in developing mouse and human pancreas. J Mol Histol. 2011;42:129-36 pubmed publisher
    ..ZAC and Zac1 (its mouse orthologue) are strongly expressed in the proliferating progenitor/stem cells in many systems and also ..
  30. Chung S, Marzban H, Aldinger K, Dixit R, Millen K, Schuurmans C, et al. Zac1 plays a key role in the development of specific neuronal subsets in the mouse cerebellum. Neural Dev. 2011;6:25 pubmed publisher
    ..Here we have used a candidate approach to identify Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, as a new player in the transcriptional ..
  31. Abramova N, Charniga C, Goderie S, Temple S. Stage-specific changes in gene expression in acutely isolated mouse CNS progenitor cells. Dev Biol. 2005;283:269-81 pubmed
    ..These data indicate that progenitor cells change during development and that adult and embryonic neural progenitor cells are intrinsically different. ..
  32. Vincent A, Gahide G, Sportouch Dukhan C, Covinhes A, Franck Miclo A, Roubille F, et al. Down-regulation of the transcription factor ZAC1 upon pre- and postconditioning protects against I/R injury in the mouse myocardium. Cardiovasc Res. 2012;94:351-8 pubmed publisher
    ..Ischaemic preconditioning (PreC) and postconditioning (PostC) reduce infarct size in animal models and human. Zac1 was identified as the only gene related to apoptosis and jointly down-regulated upon PreC and PostC...
  33. Marcelin G, Diatloff Zito C, Nicole A, Robert J. Developmental methylation program and concerted expression of Stx11 in mouse tissues. Mamm Genome. 2009;20:131-9 pubmed publisher
    ..To further characterize this region, the developmental status of DNA methylation and expression of Zac1 and Stx11 genes located within the mouse 10A1 region ortholog of human 6q24 were determined...
  34. Adnani L, Langevin L, Gautier E, Dixit R, Parsons K, Li S, et al. Zac1 Regulates the Differentiation and Migration of Neocortical Neurons via Pac1. J Neurosci. 2015;35:13430-47 pubmed publisher
    ..whether growth-associated genes influence neural lineage progression, we focused on the maternally imprinted gene Zac1. In humans, either loss or gain of ZAC1 expression is associated with reduced growth rates and intellectual ..
  35. Du X, Ounissi Benkalha H, Loder M, Rutter G, Polychronakos C. Overexpression of ZAC impairs glucose-stimulated insulin translation and secretion in clonal pancreatic beta-cells. Diabetes Metab Res Rev. 2012;28:645-53 pubmed publisher
  36. Hoffmann A, Spengler D. Transient neonatal diabetes mellitus gene Zac1 impairs insulin secretion in mice through Rasgrf1. Mol Cell Biol. 2012;32:2549-60 pubmed publisher
    The biallelic expression of the imprinted gene ZAC1/PLAGL1 underlies ? 60% of all cases of transient neonatal diabetes mellitus (TNDM) that present with low perinatal insulin secretion...
  37. Mager J, Montgomery N, de Villena F, Magnuson T. Genome imprinting regulated by the mouse Polycomb group protein Eed. Nat Genet. 2003;33:502-7 pubmed
    ..These data identify Eed as a member of a new class of trans-acting factors that regulate parent-of-origin expression at imprinted loci. ..
  38. Warzée B, Mesnil C, Hober D, Caloone D, Pirottin D, Garigliany M, et al. Viral induction of Zac1b through TLR3- and IRF3-dependent pathways. Mol Immunol. 2010;48:119-27 pubmed publisher
    b>Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways...
  39. Miro X, Zhou X, Boretius S, Michaelis T, Kubisch C, Alvarez Bolado G, et al. Haploinsufficiency of the murine polycomb gene Suz12 results in diverse malformations of the brain and neural tube. Dis Model Mech. 2009;2:412-8 pubmed publisher
    ..Here, we show that a pathway that involves Zac1 (also known as Plagl1 or Lot1) and controls neuronal proliferation is altered in mice that are heterozygous for the ..
  40. Chou W, Ho C, Tseng M, Liu S, Yen L, Huang S. Human Spot 14 protein is a p53-dependent transcriptional coactivator via the recruitment of thyroid receptor and Zac1. Int J Biochem Cell Biol. 2008;40:1826-34 pubmed publisher
    ..It does not interact directly with p53, whereas it is able to directly interact with thyroid receptor and Zac1 (zinc finger protein which regulates apoptosis and cell cycle arrest 1) using glutathione-S-transferase pull-down ..
  41. Faisal M, Kim H, Kim J. Sexual differences of imprinted genes' expression levels. Gene. 2014;533:434-8 pubmed publisher
    ..the expression levels of the following genes differ between the two sexes of mice: Peg3, Zim1, Igf2, H19 and Zac1. The expression levels of these imprinted genes are usually greater in males than in females...
  42. Royo F, Paz N, Espinosa L, McQueen P, Vellón L, Parada L. Spatial link between nucleoli and expression of the Zac1 gene. Chromosoma. 2009;118:711-22 pubmed publisher
    ..Myc, c-Met, Igf2r, Asb4, and Zac1 genes have the same radial distribution, but they are not positioned in close proximity with respect to each other...
  43. Rraklli V, Södersten E, Nyman U, Hagey D, Holmberg J. Elevated levels of ZAC1 disrupt neurogenesis and promote rapid in vivo reprogramming. Stem Cell Res. 2016;16:1-9 pubmed publisher
    The zinc finger transcription factor Zac1 is expressed in dividing progenitors of the nervous system with expression levels negatively controlled by genomic imprinting...
  44. Lanaspa M, Andres Hernando A, Rivard C, Dai Y, Li N, Berl T. ZAC1 is up-regulated by hypertonicity and decreases sorbitol dehydrogenase expression, allowing accumulation of sorbitol in kidney cells. J Biol Chem. 2009;284:19974-81 pubmed publisher
    ..A marked up-regulation was found for the zinc-finger protein ZAC1 under hypertonic stress (219-fold, p < 0.001)...