Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1

Nucleic Acids Research
Christine FeldAndreas Neubauer

Abstract

SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which >40% harbor SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI contributes to a myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets upon SKI deletion. RUNX1 ChIP-seq displays that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time the predominant co-repressive function of SKI in AML cells on a genome-wide scale and uncovers the transcription...Continue Reading

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Citations

Jul 18, 2019·Cancer Biotherapy & Radiopharmaceuticals·Shradha Mukherjee
Dec 4, 2019·Nature Biotechnology·Jeffrey M GranjaWilliam J Greenleaf
Oct 8, 2020·Cancers·Viviane PonathElke Pogge von Strandmann
Sep 23, 2019·Methods : a Companion to Methods in Enzymology·Sinja RakowCaroline Bouchard

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Datasets Mentioned

BETA
ERS420339
GSE40155
GSE107556

Methods Mentioned

BETA
RNA-seq
ChIP
FCS
immunoprecipitation
transfection
FACS
PCR
ChIP-seq
pulldown
flow cytometry

Software Mentioned

MEME SUITE
FACSDiva
GSEA
Metascape
heatmap3
scikit
SubRead
Ensembl
GCRMA
biomaRt package

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