Home LiteratureArticle Details
PMID: 17524393 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Cell shape regulates global histone acetylation in human mammary epithelial cells.

Experimental cell research ·Vol. 313 ·No. 14 ·2007-08-15 ·Pages 3066-75

Le Beyec J, Xu R, Lee SY, Nelson CM, Rizki A, Alcaraz J, Bissell MJ

Abstract

Extracellular matrix (ECM) regulates cell morphology and gene expression in vivo; these relationships are maintained in three-dimensional (3D) cultures of mammary epithelial cells. In the presence of laminin-rich ECM (lrECM), mammary epithelial cells round up and undergo global histone deacetylation, a process critical for their functional differentiation. However, it remains unclear whether lrECM-dependent cell rounding and global histone deacetylation are indeed part of a common physical-biochemical pathway. Using 3D cultures as well as nonadhesive and micropatterned substrata, here we showed that the cell 'rounding' caused by lrECM was sufficient to induce deacetylation of histones H3 and H4 in the absence of biochemical cues. Microarray and confocal analysis demonstrated that this deacetylation in 3D culture is associated with a global increase in chromatin condensation and a reduction in gene expression. Whereas cells cultured on plastic substrata formed prominent stress fibers, cells grown in 3D lrECM or on micropatterns lacked these structures. Disruption of the actin cytoskeleton with cytochalasin D phenocopied the lrECM-induced cell rounding and histone deacetylation. These results reveal a novel link between ECM-controlled cell shape and chromatin structure and suggest that this link is mediated by changes in the actin cytoskeleton.

MeSH Terms
Acetylation Actins/metabolism Cell Culture Techniques Cell Line Cell Shape Chromatin/chemistry,metabolism Cytoskeleton/metabolism Extracellular Matrix/metabolism Female Gene Expression Profiling Gene Expression Regulation Histones/metabolism Humans Mammary Glands, Human/cytology Nucleic Acid Conformation Oligonucleotide Array Sequence Analysis
Chemicals
Actins Chromatin Histones
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Le Beyec Johanne
Centre de recherche des Cordeliers, Université Piere et Marie Curie-Paris 6, ULMRS872, Paris F-75006, France.
Xu Ren
Lee Sun-Young
Nelson Celeste M
Rizki Aylin
Alcaraz Jordi
Bissell Mina J
References (71)
71 references, click to expand
  1. Histone acetylation: a switch between repressive and permissive chromatin. Second in review series on chromatin dynamics.
    EMBO Rep. 2002 Mar;3(3):224-9 PMID: 11882541
  2. Yeast heterochromatin: regulation of its assembly and inheritance by histones.
    Cell. 1998 May 1;93(3):325-8 PMID: 9590166
  3. Cooperative control of Akt phosphorylation, bcl-2 expression, and apoptosis by cytoskeletal microfilaments and microtubules in capillary endothelial cells.
    Mol Biol Cell. 2001 Oct;12(10):3087-94 PMID: 11598193
  4. The extracellular matrix in epithelial biology: shared molecules and common themes in distant phyla.
    Dev Biol. 1996 Dec 15;180(2):433-44 PMID: 8954716
  5. Protein synthesis requires cell-surface contact while nuclear events respond to cell shape in anchorage-dependent fibroblasts.
    Cell. 1980 Sep;21(2):365-72 PMID: 6157481
  6. Nuclear-cytoskeletal interactions: evidence for physical connections between the nucleus and cell periphery and their alteration by transformation.
    J Cell Biochem. 1992 Aug;49(4):357-65 PMID: 1429864
  7. Phenobarbital responsiveness as a uniquely sensitive indicator of hepatocyte differentiation status: requirement of dexamethasone and extracellular matrix in establishing the functional integrity of cultured primary rat hepatocytes.
    Exp Cell Res. 2004 Jan 15;292(2):252-64 PMID: 14697333
  8. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain.
    J Cell Biol. 2005 May 23;169(4):577-89 PMID: 15897262
  9. Tumor promoter 12-O-tetradecanoylphorbol 13-acetate, like epidermal growth factor, stimulates cell proliferation and inhibits differentiation of mouse mammary epithelial cells in culture.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1646-9 PMID: 6300862
  10. Compression-induced changes in the shape and volume of the chondrocyte nucleus.
    J Biomech. 1995 Dec;28(12):1529-41 PMID: 8666592
  11. Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype.
    Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4445-50 PMID: 16537359
  12. Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress.
    Circ Res. 2005 Mar 18;96(5):501-8 PMID: 15705964
  13. A tale of histone modifications.
    Genome Biol. 2001;2(4):REVIEWS0003 PMID: 11305943
  14. Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape.
    J Cell Sci. 1992 Dec;103 ( Pt 4):1215-22 PMID: 1487498
  15. Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2.
    J Cell Sci. 2005 Mar 15;118(Pt 6):1321-30 PMID: 15741234
  16. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer.
    Nat Genet. 2005 Apr;37(4):391-400 PMID: 15765097
  17. Extracellular matrix-regulated gene expression requires cooperation of SWI/SNF and transcription factors.
    J Biol Chem. 2007 May 18;282(20):14992-9 PMID: 17387179
  18. Modifications of chromatin structure and gene expression following induced alterations of cellular shape.
    Int J Biochem Cell Biol. 2004 Aug;36(8):1447-61 PMID: 15147724
  19. Trisomy 7p and malignant transformation of human breast epithelial cells following epidermal growth factor withdrawal.
    Cancer Res. 1996 May 1;56(9):2039-44 PMID: 8616848
  20. Substrate properties influencing ultrastructural differentiation of mammary epithelial cells in culture.
    Tissue Cell. 1979;11(1):109-19 PMID: 572104
  21. Role of cell shape in growth control.
    Nature. 1978 Jun 1;273(5661):345-9 PMID: 661946
  22. Global control of histone modification by the anaphase-promoting complex.
    Mol Cell Biol. 2003 Dec;23(24):9136-49 PMID: 14645525
  23. Integration of prolactin and glucocorticoid signaling at the beta-casein promoter and enhancer by ordered recruitment of specific transcription factors and chromatin modifiers.
    Mol Endocrinol. 2006 Oct;20(10):2355-68 PMID: 16772529
  24. Altered translatability of messenger RNA from suspended anchorage-dependent fibroblasts: reversal upon cell attachment to a surface.
    Cell. 1978 Oct;15(2):627-37 PMID: 719755
  25. Active chromatin domains are defined by acetylation islands revealed by genome-wide mapping.
    Genes Dev. 2005 Mar 1;19(5):542-52 PMID: 15706033
  26. Characterization of BCE-1, a transcriptional enhancer regulated by prolactin and extracellular matrix and modulated by the state of histone acetylation.
    Mol Cell Biol. 1998 Apr;18(4):2184-95 PMID: 9528790
  27. Characterization of the nuclear deformation caused by changes in endothelial cell shape.
    J Biomech Eng. 2004 Oct;126(5):552-8 PMID: 15648807
  28. Laminin mediates tissue-specific gene expression in mammary epithelia.
    J Cell Biol. 1995 May;129(3):591-603 PMID: 7730398
  29. Trichostatin A inhibits beta-casein expression in mammary epithelial cells.
    J Cell Biochem. 2001;83(4):660-70 PMID: 11746508
  30. Cell shape and hexose transport in normal and virus-transformed cells in culture.
    J Supramol Struct. 1977;6(1):1-12 PMID: 197315
  31. Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14711-6 PMID: 9843954
  32. Regulation of development and differentiation by the extracellular matrix.
    Development. 1993 Apr;117(4):1183-98 PMID: 8404525
  33. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells.
    Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9064-8 PMID: 1384042
  34. Nuclear compartmentalization and gene activity.
    Nat Rev Mol Cell Biol. 2000 Nov;1(2):137-43 PMID: 11253366
  35. Geometric control of cell life and death.
    Science. 1997 May 30;276(5317):1425-8 PMID: 9162012
  36. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure.
    Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):849-54 PMID: 9023345
  37. Cell adhesion status-dependent histone acetylation is regulated through intracellular contractility-related signaling activities.
    J Biol Chem. 2005 Aug 5;280(31):28357-64 PMID: 15961394
  38. The permeability of the nuclear envelope in dividing and nondividing cell cultures.
    J Cell Biol. 1990 Jul;111(1):1-8 PMID: 2365731
  39. Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity.
    J Cell Biol. 1991 Dec;115(5):1383-95 PMID: 1955479
  40. Methylation of histone H3 Lys 4 in coding regions of active genes.
    Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8695-700 PMID: 12060701
  41. Morphological changes induced by extracellular matrix are correlated with maturation of rat small hepatocytes.
    J Cell Biochem. 2002;87(1):16-28 PMID: 12210718
  42. Regulation by the extracellular matrix (ECM) of prolactin-induced alpha s1-casein gene expression in rabbit primary mammary cells: role of STAT5, C/EBP, and chromatin structure.
    J Cell Biochem. 2005 May 15;95(2):313-27 PMID: 15778982
  43. Mapping global histone acetylation patterns to gene expression.
    Cell. 2004 Jun 11;117(6):721-33 PMID: 15186774
  44. Regulating histone acetyltransferases and deacetylases.
    EMBO Rep. 2003 Oct;4(10):944-7 PMID: 14528264
  45. Simple approach to micropattern cells on common culture substrates by tuning substrate wettability.
    Tissue Eng. 2004 May-Jun;10(5-6):865-72 PMID: 15265304
  46. Epithelial cytoskeletal framework and nuclear matrix-intermediate filament scaffold: three-dimensional organization and protein composition.
    J Cell Biol. 1984 Jun;98(6):1973-84 PMID: 6202700
  47. Responses of fibroblasts to anchorage of dorsal extracellular matrix receptors.
    Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18024-9 PMID: 15601776
  48. Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology.
    Circ Res. 2002 Nov 15;91(10):877-87 PMID: 12433832
  49. Histone deacetylase inhibitors decrease proliferation and modulate cell cycle gene expression in normal mammary epithelial cells.
    Clin Cancer Res. 2000 Nov;6(11):4334-42 PMID: 11106251
  50. From laminin to lamin: regulation of tissue-specific gene expression by the ECM.
    Trends Cell Biol. 1995 Jan;5(1):1-4 PMID: 14731421
  51. Dystroglycan loss disrupts polarity and beta-casein induction in mammary epithelial cells by perturbing laminin anchoring.
    J Cell Sci. 2006 Oct 1;119(Pt 19):4047-58 PMID: 16968749
  52. A high-resolution map of active promoters in the human genome.
    Nature. 2005 Aug 11;436(7052):876-80 PMID: 15988478
  53. Translating the histone code.
    Science. 2001 Aug 10;293(5532):1074-80 PMID: 11498575
  54. Interactions between laminin and epithelial cells in intestinal health and disease.
    Expert Rev Mol Med. 2001 Sep 28;3(24):1-18 PMID: 14585148
  55. Engineering gene expression and protein synthesis by modulation of nuclear shape.
    Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1972-7 PMID: 11842191
  56. Relationship between chromatin compactness and dye uptake for in situ chromatin stained with DAPI.
    Cytometry. 2001 Jun 1;44(2):113-9 PMID: 11378861
  57. Division of labor among the alpha6beta4 integrin, beta1 integrins, and an E3 laminin receptor to signal morphogenesis and beta-casein expression in mammary epithelial cells.
    Mol Biol Cell. 1999 Sep;10(9):2817-28 PMID: 10473629
  58. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies.
    J Cell Biol. 1997 Apr 7;137(1):231-45 PMID: 9105051
  59. Engineering cell shape and function.
    Science. 1994 Apr 29;264(5159):696-8 PMID: 8171320
  60. Tissue architecture: the ultimate regulator of breast epithelial function.
    Curr Opin Cell Biol. 2003 Dec;15(6):753-62 PMID: 14644202
  61. Shear stress-mediated chromatin remodeling provides molecular basis for flow-dependent regulation of gene expression.
    Circ Res. 2003 Jul 25;93(2):155-61 PMID: 12805238
  62. Histone modifications, chromatin structure, and the nuclear matrix.
    J Cell Biochem. 1996 Aug;62(2):149-57 PMID: 8844394
  63. Activation of the p21WAF1/CIP1 promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) through the Sp1 sites.
    Oncogene. 2000 Nov 23;19(50):5712-9 PMID: 11126357
  64. DNA methylation control of tissue polarity and cellular differentiation in the mammary epithelium.
    Exp Cell Res. 2004 Aug 1;298(1):122-32 PMID: 15242767
  65. Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility.
    FASEB J. 2005 Jun;19(8):966-8 PMID: 15772115
  66. Brd4 is required for recovery from antimicrotubule drug-induced mitotic arrest: preservation of acetylated chromatin.
    Mol Biol Cell. 2006 Feb;17(2):814-23 PMID: 16339075
  67. A new diploid nontumorigenic human breast epithelial cell line isolated and propagated in chemically defined medium.
    In Vitro Cell Dev Biol. 1987 Mar;23(3):181-8 PMID: 3558253
  68. How does the extracellular matrix direct gene expression?
    J Theor Biol. 1982 Nov 7;99(1):31-68 PMID: 6892044
  69. Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12378-82 PMID: 7528920
  70. Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer.
    Cancer Res. 2006 Jul 15;66(14):7095-102 PMID: 16849555
  71. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation.
    Nature. 2000 Nov 2;408(6808):106-11 PMID: 11081517
Article Info
Journal
Experimental cell research
Abbr.
Exp Cell Res
ISSN
0014-4827
DOI
10.1016/j.yexcr.2007.04.022
Published
2007-08-15
Epub
2007-00-27
Pages
3066-75
Language
English
Region
United States
NLM ID
0373226
PMCID
PMC2040058
Subset
IM
Grants
NCI NIH HHS · CA 64786 · United States
NCI NIH HHS · R37 CA064786 · United States
NCI NIH HHS · R01 CA064786-09 · United States
NCI NIH HHS · CA 57621 · United States
NCI NIH HHS · R01 CA057621 · United States
NCI NIH HHS · R01 CA064786 · United States
External Links
PubMed source DOI: 10.1016/j.yexcr.2007.04.022 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: [email protected]

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