Histone deacetylation is involved in activation of CXCL10 upon IFNgamma stimulation.
Histone deacetylase (HDAC) activity is commonly associated with transcriptional repression. However, there is also evidence for a function in transcriptional activation. Previous studies have demonstrated a fundamental role of deacetylase activity in IFNa-responsive gene transcription. In the case of type II IFN (IFNgamma) results are controversial: some genes require HDAC activity, while transcription of others is repressed by HDAC. To investigate the effect of HDAC on transcription of an IFNgamma-activated gene, real-time PCR was used to measure CXCL10 mRNA in Hela cells stimulated with IFNgamma in the presence or absence of the HDAC inhibitor TSA. Chromatin imunoprecipitation combined with real-time PCR was used to check acetylation of histone H4 and recruitment of the STAT1 complex to the ISRE locus of the CXCL10 gene. Activation of CXCL10 transcription in response to IFNgamma was paralleled by a decrease in histone H4 acetylation and an increase in recruitment of the STAT1 complex to the CXCL10 ISRE locus. The transcription of CXCL10 and histone H4 deacetylation were blocked by TSA, but the latter had no obvious affect on recruitment of the STAT1 complex. Our data indicate that IFNgamma and STAT-dependent gene transcription requires the participation of HDAC, as does the IFNalpha-STAT pathway.
Guo
Jin-Jun
JJ
Institute for Viral Hepatitis, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing University of Medical Sciences, Chong Qing, China.
Li
Qing-ling
QL
Zhang
Jun
J
Huang
Ai-Long
AL
D000107:Acetylation; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; D006655:Histone Deacetylases