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SATB2 induces transcriptional programs in melanoma that lead to metastatic behavior [ChIP-Seq]

UID: 10778

Author(s): van Rooijen, Ellen, Yang, Song, Zhou, Yi, Trompouki, Eirini, Zon, Leonard I.

Description
Summary from the GEO: "We report the distribution of human SATB2 in a primary zebrafish melanoma that overexpresses human SATB2, and H3K27Ac histone marks in zebrafish melanomas overexpressing either EGFP (control) or human SATB2."

Overall design from the GEO: "Examining SATB2 bound regions, and H3K27Ac-bound (super) enhancers in zebrafish melanomas."

Abstract summary: "Recent genomic and scRNA-seq analyses of melanoma demonstrated a lack of recurrent genetic drivers of metastasis, while identifying common transcriptional states correlating with invasion or drug resistance. To test whether transcriptional adaptation can drive melanoma progression, we made use of a zebrafish mitfa:BRAFV600E;tp53-/-model, in which malignant progression is characterized by minimal genetic evolution. We undertook an overexpression-screen of 80 epigenetic/transcriptional regulators and found neural crest-mesenchyme developmental regulator SATB2 to accelerate aggressive melanoma development. Its overexpression induces invadopodia formation and invasion in zebrafish tumors and human melanoma cell lines. SATB2 binds and activates neural crest-regulators, including pdgfab and snai2. The transcriptional program induced by SATB2 overlaps with known MITFlowAXLhigh and AQP1+NGFR1high drug-resistant states and functionally drives enhanced tumor propagation and resistance to Vemurafenib in vivo. In summary, we show that melanoma transcriptional rewiring by SATB2 to a neural crest mesenchyme-like program can drive invasion and drug resistance in autochthonous tumors."
Subject of Study
Danio rerio
Subject(s)
Histones
Matrix Attachment Region Binding Proteins
Melanoma
Transcription Factors
Access via GEO

BED and Plain Text files of genome binding/occupancy profiling by high throughput sequencing
Accession #: GSE77921

Access via SRA

ChIP Sequencing data from 6 samples
Accession #: SRP070126

Access via BioProject

Additional information about the overall inititative.
Accession #: PRJNA312108

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA and BioProject databases provide open access to these files. SRA and/or tar files can be downloaded directly from the site or viewed in the NCBI SRA Run Selector (link at bottom of page).
Associated Publications
Fazio M, van Rooijen E, Dang M, et al. SATB2 induction of a neural crest mesenchyme-like program drives melanoma invasion and drug resistance. eLife. 2021; 10:e64370.
Data Type
Genomic
Equipment Used
Illumina Genome Analyzer II

The Genome Analyzer supports a wide range of applications, including whole-genome and candidate region resequencing, transcriptome analysis, small RNA discovery, methylation profi ling, and protein-nucleic acid interaction analysis at a genome-wide scale.

Illumina HiSeq 2500

High throughput sequencing system

Software Used
SRA Toolkit

The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.

Dataset Format(s)
Plain Text, SRA, TAR, BED
Data Tool(s)
ChIP Seq
Dataset Size
3.8 MB (TAR of BED, TXT), 5.2 GB (SRA)
Data Catalog Record Updated
2023-12-07