TY - JOUR
T1 - Overexpression of histone deacetylases in cancer cells is controlled by interplay of transcription factors and epigenetic modulators
AU - Yang, Hui
AU - Salz, Tal
AU - Zajac-Kaye, Maria
AU - Liao, Daiqing
AU - Huang, Suming
AU - Qiu, Yi
N1 - Publisher Copyright:
© FASEB.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Histone deacetylases (HDACs) that deacetylate histone and nonhistone proteins play crucial roles in a variety of cellular processes. The overexpression of HDACs is reported in many cancer types and is directly linked to accelerated cell proliferation and survival. However, little is known about how HDAC expression is regulated in cancer cells. In this study, we found that HDAC1 and HDAC2 promoters are regulated through collaborative binding of transcription factors Sp1/Sp3 and epigenetic modulators, including histone H3K4 methyltransferase SET1 and histone acetyltransferase p300, whose levels are also elevated in colon cancer cell lines and patient samples. Interestingly, Sp1 and Sp3 differentially regulate HDAC1 and HDAC2 promoter activity. In addition, Sp1/Sp3 recruits SET1 and p300 to the promoters. SET1 knockdown (KD) results in a loss of the H3K4 trimethylation mark at the promoters, as well as destabilizes p300 at the promoters. Conversely, p300 also influences SET1 recruitment and H3K4me3 level, indicating a crosstalk between p300 and SET1. Further, SET1 KD reduces Sp1 binding to the HDAC1 promoter through the increase of Sp1 acetylation.
AB - Histone deacetylases (HDACs) that deacetylate histone and nonhistone proteins play crucial roles in a variety of cellular processes. The overexpression of HDACs is reported in many cancer types and is directly linked to accelerated cell proliferation and survival. However, little is known about how HDAC expression is regulated in cancer cells. In this study, we found that HDAC1 and HDAC2 promoters are regulated through collaborative binding of transcription factors Sp1/Sp3 and epigenetic modulators, including histone H3K4 methyltransferase SET1 and histone acetyltransferase p300, whose levels are also elevated in colon cancer cell lines and patient samples. Interestingly, Sp1 and Sp3 differentially regulate HDAC1 and HDAC2 promoter activity. In addition, Sp1/Sp3 recruits SET1 and p300 to the promoters. SET1 knockdown (KD) results in a loss of the H3K4 trimethylation mark at the promoters, as well as destabilizes p300 at the promoters. Conversely, p300 also influences SET1 recruitment and H3K4me3 level, indicating a crosstalk between p300 and SET1. Further, SET1 KD reduces Sp1 binding to the HDAC1 promoter through the increase of Sp1 acetylation.
UR - http://www.scopus.com/inward/record.url?scp=84907697952&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907697952&partnerID=8YFLogxK
U2 - 10.1096/fj.14-250654
DO - 10.1096/fj.14-250654
M3 - Article
C2 - 24948597
AN - SCOPUS:84907697952
SN - 0892-6638
VL - 28
SP - 4265
EP - 4279
JO - FASEB Journal
JF - FASEB Journal
IS - 10
ER -