Integration of genome-wide of Stat3 binding and epigenetic modification mapping with transcriptome reveals novel Stat3 target genes in glioma cells
PBN-AR
Instytucja
Instytut Podstaw Informatyki Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
ISSN
1874-9399
EISSN
Wydawca
Elsevier
Rok publikacji
2014
Numer zeszytu
11
Strony od-do
1341–1350
Numer tomu
1839
Identyfikator DOI
Liczba arkuszy
Autorzy
(liczba autorów: 11)
Pozostali autorzy
+ 10
Słowa kluczowe
angielski
Stat3
Glioma
Whole genome Stat3 occupancy
Epigenetic modification
Transcriptome–epigenome interaction
Stat3 gene regulatory network
Streszczenia
Język
angielski
Treść
Background Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many human tumors, including gliomas, and regulates the expression of genes implicated in proliferation, survival, apoptosis, angiogenesis and immune regulation. Only a small fraction of those genes has been proven to be direct STAT3 targets. In gliomas, STAT3 can play tumor suppressive or oncogenic roles depending on the tumor genetic background with target genes being largely unknown. Results We used chromatin immunoprecipitation, promoter microarrays and deep sequencing to assess the genome-wide occupancy of phospho (p)-Stat3 and epigenetic modifications of H3K4me3 and H3ac in C6 glioma cells. This combined assessment identified a list of 1200 genes whose promoters have both Stat3 binding sites and epigenetic marks characteristic for actively transcribed genes. The Stat3 and histone markings data were also intersected with a set of microarray data from C6 glioma cells after inhibition of Jak2/Stat3 signaling. Subsequently, we found 284 genes characterized by p-Stat3 occupancy, activating histone marks and transcriptional changes. Novel genes were screened for their potential involvement in oncogenesis, and the most interesting hits were verified by ChIP-PCR and STAT3 knockdown in human glioma cells. Conclusions Non-random association between silent genes, histone marks and p-Stat3 binding near transcription start sites was observed, consistent with its repressive role in transcriptional regulation of target genes in glioma cells with specific genetic background.
Inne
System-identifier
PX-56988deb810641ecf91929a1
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