Home LiteratureArticle Details
PMID: 11118214 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

P/CAF-mediated acetylation regulates the function of the basic helix-loop-helix transcription factor TAL1/SCL.

The EMBO journal ·Vol. 19 ·No. 24 ·2000-12-15 ·Pages 6792-803

Huang S, Qiu Y, Shi Y, Xu Z, Brandt SJ

Abstract

The basic helix-loop-helix transcription factor TAL1 (or SCL) is a critical regulator of hematopoietic and vascular development and is misexpressed in the majority of patients with T-cell acute lymphoblastic leukemia. We found previously that TAL1 could interact with transcriptional co-activator and co-repressor complexes possessing histone acetyltransferase and deacetylase activities, respectively. Here, we report that TAL1 is subject to acetylation in vivo and can be acetylated by p300 and the p300/CBP-associated factor P/CAF in vitro. P/CAF-mediated acetylation, which mapped to a lysine-rich motif in the loop region, increased TAL1 binding to DNA while selectively inhibiting its interaction with the transcriptional co-repressor mSin3A. Furthermore, P/CAF protein, TAL1-P/CAF interaction and TAL1 acetylation increased significantly in murine erythroleukemia cells induced to differentiate in culture, while enforced expression of an acetylation-defective P/CAF mutant inhibited endogenous TAL1 acetylation, TAL1 DNA-binding activity, TAL1-directed transcription and terminal differentiation of these cells. These results reveal a novel mechanism by which TAL1 activity is regulated and implicate acetylation of this transcription factor in promotion of erythroid differentiation.

MeSH Terms
Acetylation Acetyltransferases/metabolism Animals Basic Helix-Loop-Helix Transcription Factors Binding Sites Cell Cycle Proteins/metabolism Cell Differentiation Conserved Sequence DNA-Binding Proteins/chemistry,metabolism HeLa Cells Helix-Loop-Helix Motifs Histone Acetyltransferases Humans Leukemia, Erythroblastic, Acute Lysine Mice Protein Biosynthesis Proto-Oncogene Proteins Recombinant Proteins/metabolism T-Cell Acute Lymphocytic Leukemia Protein 1 Transcription Factors/chemistry,metabolism Transfection Tumor Cells, Cultured p300-CBP Transcription Factors
Chemicals
Basic Helix-Loop-Helix Transcription Factors Cell Cycle Proteins DNA-Binding Proteins Proto-Oncogene Proteins Recombinant Proteins T-Cell Acute Lymphocytic Leukemia Protein 1 Tal1 protein, mouse Transcription Factors TAL1 protein, human Acetyltransferases Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor Lysine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Huang S
Departments of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Qiu Y
Shi Y
Xu Z
Brandt S J
References (94)
94 references, click to expand
  1. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP.
    Nature. 1995 Mar 2;374(6517):85-8 PMID: 7870179
  2. Histone acetylation and transcriptional regulatory mechanisms.
    Genes Dev. 1998 Mar 1;12(5):599-606 PMID: 9499396
  3. Enhanced megakaryocyte and erythroid development from normal human CD34(+) cells: consequence of enforced expression of SCL.
    Blood. 1998 May 15;91(10):3756-65 PMID: 9573012
  4. Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein.
    Oncogene. 1998 May 14;16(19):2549-56 PMID: 9627120
  5. Differential roles of p300 and PCAF acetyltransferases in muscle differentiation.
    Mol Cell. 1997 Dec;1(1):35-45 PMID: 9659901
  6. Histone-like TAFs within the PCAF histone acetylase complex.
    Cell. 1998 Jul 10;94(1):35-44 PMID: 9674425
  7. E1A directly binds and regulates the P/CAF acetyltransferase.
    EMBO J. 1998 Aug 3;17(15):4469-77 PMID: 9687513
  8. Acetylation and modulation of erythroid Krüppel-like factor (EKLF) activity by interaction with histone acetyltransferases.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9855-60 PMID: 9707565
  9. DNA damage activates p53 through a phosphorylation-acetylation cascade.
    Genes Dev. 1998 Sep 15;12(18):2831-41 PMID: 9744860
  10. The LAZ3(BCL-6) oncoprotein recruits a SMRT/mSIN3A/histone deacetylase containing complex to mediate transcriptional repression.
    Nucleic Acids Res. 1998 Oct 15;26(20):4645-51 PMID: 9753732
  11. Roles of histone acetyltransferases and deacetylases in gene regulation.
    Bioessays. 1998 Aug;20(8):615-26 PMID: 9780836
  12. Acetylation of HMG I(Y) by CBP turns off IFN beta expression by disrupting the enhanceosome.
    Mol Cell. 1998 Oct;2(4):457-67 PMID: 9809067
  13. TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3.
    Mol Cell Biol. 1998 Dec;18(12):6939-50 PMID: 9819382
  14. ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors.
    Mol Cell Biol. 1998 Dec;18(12):7176-84 PMID: 9819404
  15. Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO.
    Mol Cell Biol. 1998 Dec;18(12):7185-91 PMID: 9819405
  16. Regulation of activity of the transcription factor GATA-1 by acetylation.
    Nature. 1998 Dec 10;396(6711):594-8 PMID: 9859997
  17. Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates.
    J Biol Chem. 1999 Jan 15;274(3):1189-92 PMID: 9880483
  18. p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage.
    Mol Cell Biol. 1999 Feb;19(2):1202-9 PMID: 9891054
  19. Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction with nucleosomes.
    Mol Cell Biol. 1999 May;19(5):3466-73 PMID: 10207070
  20. CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites.
    Mol Cell Biol. 1999 May;19(5):3496-505 PMID: 10207073
  21. Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase.
    Cell. 1999 Sep 3;98(5):675-86 PMID: 10490106
  22. Both TEL and AML-1 contribute repression domains to the t(12;21) fusion protein.
    Mol Cell Biol. 1999 Oct;19(10):6566-74 PMID: 10490596
  23. p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein.
    Oncogene. 1999 Sep 2;18(35):4958-67 PMID: 10490830
  24. p300 stimulates transcription instigated by ligand-bound thyroid hormone receptor at a step subsequent to chromatin disruption.
    EMBO J. 1999 Oct 15;18(20):5634-52 PMID: 10523307
  25. The SCL gene product: a positive regulator of erythroid differentiation.
    EMBO J. 1992 Nov;11(11):4073-81 PMID: 1396592
  26. HIV-1 tat transcriptional activity is regulated by acetylation.
    EMBO J. 1999 Nov 1;18(21):6106-18 PMID: 10545121
  27. PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner.
    Mol Cell Biol. 1999 Dec;19(12):8136-45 PMID: 10567539
  28. Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity.
    Curr Biol. 1999 Dec 16-30;9(24):1489-92 PMID: 10607594
  29. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms.
    Mol Cell Biol. 2000 Jan;20(2):429-40 PMID: 10611221
  30. Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program.
    Mol Cell. 1999 Nov;4(5):725-34 PMID: 10619020
  31. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A.
    Nature. 1996 Jul 25;382(6589):319-24 PMID: 8684459
  32. ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex.
    Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10860-5 PMID: 9724795
  33. A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system.
    J Biol Chem. 1995 Apr 14;270(15):8730-8 PMID: 7721778
  34. Coordinate expression and developmental role of Id2 protein and TAL1/E2A heterodimer in erythroid progenitor differentiation.
    Blood. 1995 Jul 1;86(1):164-75 PMID: 7540882
  35. Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7075-9 PMID: 7624372
  36. CBP-induced stimulation of c-Fos activity is abrogated by E1A.
    EMBO J. 1995 Oct 2;14(19):4758-62 PMID: 7588605
  37. Targeting chromatin disruption: Transcription regulators that acetylate histones.
    Cell. 1996 Mar 22;84(6):817-9 PMID: 8601304
  38. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation.
    Cell. 1996 Mar 22;84(6):843-51 PMID: 8601308
  39. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.
    Science. 1996 Apr 19;272(5260):408-11 PMID: 8602529
  40. Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation.
    Mol Cell Biol. 1996 Oct;16(10):5737-43 PMID: 8816487
  41. Tal-1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha.
    EMBO J. 1996 Oct 1;15(19):5160-6 PMID: 8895560
  42. T-cell-directed TAL-1 expression induces T-cell malignancies in transgenic mice.
    Cancer Res. 1996 Nov 15;56(22):5113-9 PMID: 8912842
  43. The transcriptional coactivators p300 and CBP are histone acetyltransferases.
    Cell. 1996 Nov 29;87(5):953-9 PMID: 8945521
  44. The CBP co-activator is a histone acetyltransferase.
    Nature. 1996 Dec 19-26;384(6610):641-3 PMID: 8967953
  45. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity.
    Cell. 1996 Dec 27;87(7):1261-70 PMID: 8980232
  46. Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL.
    J Biol Chem. 1997 Feb 14;272(7):4576-81 PMID: 9020185
  47. Mist1: a novel basic helix-loop-helix transcription factor exhibits a developmentally regulated expression pattern.
    Dev Biol. 1997 Feb 1;182(1):101-13 PMID: 9073453
  48. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins.
    EMBO J. 1997 Jun 2;16(11):3145-57 PMID: 9214632
  49. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.
    Cell. 1997 Aug 8;90(3):569-80 PMID: 9267036
  50. Acetylation of general transcription factors by histone acetyltransferases.
    Curr Biol. 1997 Sep 1;7(9):689-92 PMID: 9285713
  51. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.
    Cell. 1997 Aug 22;90(4):595-606 PMID: 9288740
  52. CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein.
    Cancer Res. 1997 Sep 1;57(17):3693-6 PMID: 9288775
  53. Retroviral-mediated transfer of the green fluorescent protein gene into murine hematopoietic cells facilitates scoring and selection of transduced progenitors in vitro and identification of genetically modified cells in vivo.
    Blood. 1997 Sep 1;90(5):1777-86 PMID: 9292510
  54. Steroid receptor coactivator-1 is a histone acetyltransferase.
    Nature. 1997 Sep 11;389(6647):194-8 PMID: 9296499
  55. Histone acetylation in chromatin structure and transcription.
    Nature. 1997 Sep 25;389(6649):349-52 PMID: 9311776
  56. The histone acetyltransferase activity of human GCN5 and PCAF is stabilized by coenzymes.
    J Biol Chem. 1997 Oct 24;272(43):27253-8 PMID: 9341171
  57. Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL.
    Nat Genet. 1998 Feb;18(2):126-35 PMID: 9462740
  58. Role of the histone deacetylase complex in acute promyelocytic leukaemia.
    Nature. 1998 Feb 19;391(6669):811-4 PMID: 9486654
  59. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia.
    Nature. 1998 Feb 19;391(6669):815-8 PMID: 9486655
  60. The basic helix-loop-helix transcription factor Mist1 functions as a transcriptional repressor of myoD.
    EMBO J. 1998 Mar 2;17(5):1412-22 PMID: 9482738
  61. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation.
    Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2061-6 PMID: 9482838
  62. The coregulator exchange in transcriptional functions of nuclear receptors.
    Genes Dev. 2000 Jan 15;14(2):121-41 PMID: 10652267
  63. Correlations among amino acid sites in bHLH protein domains: an information theoretic analysis.
    Mol Biol Evol. 2000 Jan;17(1):164-78 PMID: 10666716
  64. Regulation of E2F1 activity by acetylation.
    EMBO J. 2000 Feb 15;19(4):662-71 PMID: 10675335
  65. mSin3A regulates murine erythroleukemia cell differentiation through association with the TAL1 (or SCL) transcription factor.
    Mol Cell Biol. 2000 Mar;20(6):2248-59 PMID: 10688671
  66. The proneural gene amos promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.
    Neuron. 2000 Jan;25(1):57-67 PMID: 10707972
  67. amos, a proneural gene for Drosophila olfactory sense organs that is regulated by lozenge.
    Neuron. 2000 Jan;25(1):69-78 PMID: 10707973
  68. Acetylation: a regulatory modification to rival phosphorylation?
    EMBO J. 2000 Mar 15;19(6):1176-9 PMID: 10716917
  69. The PCAF acetylase complex as a potential tumor suppressor.
    Biochim Biophys Acta. 2000 Mar 27;1470(2):M37-53 PMID: 10722926
  70. E2F family members are differentially regulated by reversible acetylation.
    J Biol Chem. 2000 Apr 14;275(15):10887-92 PMID: 10753885
  71. Acetylation of novel sites in the nucleosomal binding domain of chromosomal protein HMG-14 by p300 alters its interaction with nucleosomes.
    J Biol Chem. 2000 Apr 14;275(15):11514-20 PMID: 10753971
  72. Acetylation regulates transcription factor activity at multiple levels.
    Mol Cell. 2000 Apr;5(4):745-51 PMID: 10882110
  73. HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF.
    Mol Cell. 2000 Mar;5(3):589-95 PMID: 10882143
  74. Changes in histone acetylation and RNA synthesis in the spleen of polycythemic mouse after erythropoietin injection.
    Biochim Biophys Acta. 1969 Dec 16;195(2):396-400 PMID: 5366928
  75. Increase in histone acetylation and transitions in histone variants during Friend cell differentiation.
    Exp Cell Res. 1984 Nov;155(1):222-31 PMID: 6593226
  76. Splenic erythroblasts in anemia-inducing Friend disease: a source of cells for studies of erythropoietin-mediated differentiation.
    J Cell Physiol. 1984 Dec;121(3):526-32 PMID: 6501430
  77. Molecular and cellular mechanisms of leukemic hemopoietic cell differentiation: an analysis of the Friend system.
    Anticancer Res. 1985 Jan-Feb;5(1):81-99 PMID: 3888045
  78. Firefly luciferase gene: structure and expression in mammalian cells.
    Mol Cell Biol. 1987 Feb;7(2):725-37 PMID: 3821727
  79. A direct link between core histone acetylation and transcriptionally active chromatin.
    EMBO J. 1988 May;7(5):1395-402 PMID: 3409869
  80. Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript.
    Proc Natl Acad Sci U S A. 1989 Mar;86(6):2031-5 PMID: 2467296
  81. Involvement of the TCL5 gene on human chromosome 1 in T-cell leukemia and melanoma.
    Proc Natl Acad Sci U S A. 1989 Jul;86(13):5039-43 PMID: 2740341
  82. A vector for expressing GAL4(1-147) fusions in mammalian cells.
    Nucleic Acids Res. 1989 Sep 25;17(18):7539 PMID: 2798115
  83. The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein.
    EMBO J. 1990 Feb;9(2):415-24 PMID: 2303035
  84. Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors.
    Nature. 1990 Aug 30;346(6287):858-61 PMID: 2392153
  85. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.
    J Biol Chem. 1990 Oct 5;265(28):17174-9 PMID: 2211619
  86. TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11416-20 PMID: 1763056
  87. Molecular characterization of NSCL, a gene encoding a helix-loop-helix protein expressed in the developing nervous system.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):38-42 PMID: 1729708
  88. NSCL-2: a basic domain helix-loop-helix gene expressed in early neurogenesis.
    Cell Growth Differ. 1992 Mar;3(3):143-8 PMID: 1633105
  89. Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins.
    Mol Cell Biol. 1994 Feb;14(2):1256-65 PMID: 8289805
  90. The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis.
    Blood. 1994 Mar 1;83(5):1200-8 PMID: 8118024
  91. Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation.
    Cell. 1994 May 6;77(3):451-9 PMID: 8181063
  92. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia.
    EMBO J. 1994 Oct 17;13(20):4831-9 PMID: 7957052
  93. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL.
    Nature. 1995 Feb 2;373(6513):432-4 PMID: 7830794
  94. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.
    Nature. 1995 Mar 2;374(6517):81-4 PMID: 7870178
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.24.6792
Published
2000-12-15
Pages
6792-803
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305888
Subset
IM
Grants
NCI NIH HHS · P30 CA068485 · United States
NHLBI NIH HHS · R01 HL049118 · United States
NHLBI NIH HHS · R01 HL49118 · United States
External Links
PubMed source DOI: 10.1093/emboj/19.24.6792 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2