Chromatin modification requirements for 15-lipoxygenase-1 transcriptional reactivation in colon cancer cells.
15-Lipoxygenase-1 (15-LOX-1) contributes significantly to inflammation regulation and terminal cell differentiation. 15-LOX-1 is transcriptionally silenced in cancer cells, and its transcriptional reactivation (e.g. via histone deacetylase inhibitors (HDACIs)) is essential for restoring terminal cell differentiation to cancer cells. STAT-6 acetylation via the histone acetyltransferase KAT3B has been proposed to be necessary for 15-LOX-1 transcriptional activation. However, the exact mechanism underlying 15-LOX-1 transcriptional reactivation in cancer cells is still undefined, especially in regard to the contribution of 15-LOX-1 promoter histone modifications. We therefore examined the relative mechanistic contributions of 15-LOX-1 promoter histone modifications and STAT-6 to 15-LOX-1 transcriptional reactivation by HDACIs in colon cancer cells. We found that: 1) histone H3 and H4 acetylation in the 15-LOX-1 promoter through KAT3B was critical to 15-LOX-1 transcriptional activation; 2) 15-LOX-1 transcription was activated independently from STAT-6; and 3) dimethyl-histone H3 lysine 9 (H3K9me2) demethylation in the 15-LOX-1 promoter via the histone lysine demethylase KDM3A was an early and specific histone modification and was necessary for activation of transcription. These findings demonstrate that histone modification in the 15-LOX-1 promoter is important to 15-LOX-1 transcriptional silencing in colon cancer cells and that HDACIs can activate gene transcription via KDM3A demethylation of H3K9me2.
Zuo
Xiangsheng
X
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Morris
Jeffrey S
JS
Shureiqi
Imad
I
D000107:Acetylation; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
D002843:Chromatin; D006657:Histones; D034741:RNA, Small Interfering; D050800:STAT6 Transcription Factor; D001093:Arachidonate 15-Lipoxygenase
Curr Biol. 2004 Jul 27;14(14):R546-51
15268870
Cancer Res. 2001 Jun 15;61(12):4879-84
11406566
FEBS Lett. 2001 Jan 26;489(1):51-4
11231012
Cell. 1996 Nov 29;87(5):953-9
8945521
Trends Immunol. 2007 Apr;28(4):176-83
17337246
J Invest Dermatol. 2005 Nov;125(5):1045-52
16297208
Biochem Biophys Res Commun. 1991 Oct 15;180(1):98-104
1930242
Prostaglandins Leukot Essent Fatty Acids. 2006 Apr;74(4):235-45
16556493
FASEB J. 2008 Jun;22(6):1981-92
18198215
Cell. 1997 May 16;89(4):597-606
9160751
J Natl Cancer Inst. 2000 Jul 19;92(14):1136-42
10904086
Oncogene. 2006 Feb 23;25(8):1225-41
16288226
Nat Rev Drug Discov. 2006 Sep;5(9):769-84
16955068
Cell. 2006 May 5;125(3):483-95
16603237
Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6148-52
9177185
Neoplasia. 2007 Nov;9(11):917-26
18030360
Am J Respir Cell Mol Biol. 2000 Feb;22(2):226-34
10657944
J Immunol. 2003 Dec 15;171(12):6856-65
14662892
J Biol Chem. 2001 Nov 16;276(46):42753-60
11509556
Nature. 2005 Aug 25;436(7054):1103-6
16121170
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9968-73
12909723
Biochem Biophys Res Commun. 1989 Apr 28;160(2):954-60
2719708
Carcinogenesis. 2003 Feb;24(2):243-7
12584173
Carcinogenesis. 2001 Jan;22(1):187-91
11159758
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5152-7
11320251
Mol Ther. 2008 May;16(5):886-892
28178489
Carcinogenesis. 1999 Oct;20(10):1985-95
10506115
Genes Dev. 2006 Nov 15;20(22):3089-103
17085482
Prostaglandins Leukot Essent Fatty Acids. 2004 Jan;70(1):7-15
14643174
Cancer Res. 2005 Dec 15;65(24):11486-92
16357157
Mol Cancer Ther. 2005 Nov;4(11):1740-6
16275995
Endocr Rev. 2005 Apr;26(2):147-70
15479858
Nature. 1998 Sep 24;395(6700):392-5
9759730
Exp Cell Res. 2004 Jul 1;297(1):61-7
15194425
FASEB J. 2007 Mar;21(3):743-53
17167069
Cancer Res. 2002 Feb 15;62(4):1178-83
11861401
Blood. 1998 Oct 1;92(7):2503-10
9746791
Cancer Res. 2004 Dec 1;64(23):8778-81
15574791
Nat Rev Genet. 2007 Nov;8(11):829-33
17909537
Mol Cell Biol. 1996 Oct;16(10):5811-20
8816495
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:263-90
12432923
Cancer Res. 2005 Sep 15;65(18):8442-7
16166323
Cancer Res. 2002 Sep 1;62(17):4916-21
12208741
Prostaglandins Leukot Essent Fatty Acids. 2005 Aug;73(2):77-83
15996861
Am J Respir Cell Mol Biol. 1998 May;18(5):662-9
9569236
FEBS Lett. 2000 Feb 11;467(2-3):341-7
10675566
Curr Opin Genet Dev. 2006 Apr;16(2):125-36
16503131
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13375-80
10557328
Nature. 1996 Dec 19-26;384(6610):641-3
8967953
Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49
16261189
Ann Surg. 2005 Jun;241(6):941-6; discussion 946-7
15912043