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Series GSE180879 Query DataSets for GSE180879
Status Public on Jul 27, 2021
Title Analysis of long and short enhancers in melanoma cell states
Organisms Homo sapiens; synthetic construct
Experiment type Other
Summary Understanding how enhancers drive cell type specificity and efficiently identifying them is essential for the development of innovative therapeutic strategies. In melanoma, the melanocytic (MEL) and the mesenchymal-like (MES) states present themselves with different responses to therapy, making the identification of specific enhancers highly relevant. Using massively parallel reporter assay (MPRA) in a panel of patient-derived melanoma lines (MM lines), we set to identify and decipher melanoma enhancers by first focusing on regions with state specific H3K27 acetylation close to differentially expressed genes. A more in-depth evaluation of those regions was then pursued by investigating the activity of ATAC-seq peaks found therein along with a full tiling of the acetylated regions with 190 bp sequences. Activity was observed in more than 60% of the selected regions and we were able to precisely locate the active regions within ATAC-seq peaks. Comparison of sequence content with activity, using the deep learning model DeepMEL2, revealed that AP-1 alone is responsible for the MES enhancer activity, while SOX and MITF both influence MEL enhancer activity with SOX being required to achieve high levels of activity. Overall, our MPRA assays shed light on the relationship between long and short sequences in terms of their sequence content, enhancer activity, and specificity as reporters across melanoma cell states.
 
Overall design Eight MPRA libraries are used in this study, including 7 CHEQ-seq libraries and 1 STARR-seq library. For each CHEQ-seq library an enhancer - barcode assignment is done by sequencing of the plasmid library with PacBio or Illumina sequencing. Libraries CHEQ-seq 5' H3K27ac, CHEQ-seq Intron H3K27ac, CHEQ-seq ATAC and STARR-seq ATAC are transfected in seven cell lines. Libraries CHEQ-seq enhancer tiling A and B are transfected in 5 cell lines. Library CHEQ-seq SOX10-KD is transfected in one cell line. Library CHEQ-seq SOX-MITF combinations is transfected in 3 cell lines.
 
Contributor(s) Mauduit D, Minnoye L, Taskiran II, de Waegeneer M, Christiaens V, Hulselmans G, Demeulemeester J, Wouters J, Aerts S
Citation(s) 34874265
Submission date Jul 26, 2021
Last update date Jan 07, 2022
Contact name Gert Hulselmans
E-mail(s) gert.hulselmans@kuleuven.be
Organization name VIB
Department Center for Brain and Disease Research
Lab Laboratory of Computational Biology
Street address Herestraat 49 PO Box 602
City Leuven
ZIP/Postal code 3000
Country Belgium
 
Platforms (6)
GPL17769 Illumina MiSeq (synthetic construct)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (112)
GSM5474120 Enhancer - barcode assignmennt CHEQ-seq 5' H3K27ac
GSM5474121 Enhancer - barcode assignmennt CHEQ-seq Intron H3K27ac
GSM5474122 Enhancer - barcode assignmennt CHEQ-seq ATAC
Relations
BioProject PRJNA749864
SRA SRP329966

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE180879_CHEQ-seq_5p_H3K27ac_enh-BC_list.tsv.gz 7.7 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_5p_H3K27ac_processed.tsv.gz 2.5 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_ATAC_enh-BC_list.tsv.gz 10.5 Mb (ftp)(http) TSV
GSE180879_CHEQ-seq_ATAC_processed.tsv.gz 3.1 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_Enhancer-tiling-A_enh-BC_list.tsv.gz 558.6 Mb (ftp)(http) TSV
GSE180879_CHEQ-seq_Enhancer-tiling-B_enh-BC_list.tsv.gz 501.0 Mb (ftp)(http) TSV
GSE180879_CHEQ-seq_Enhancer_tiling_A_processed.tsv.gz 307.9 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_Enhancer_tiling_B_processed.tsv.gz 289.0 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_Intron_H3K27ac_enh-BC_list.tsv.gz 181.7 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_Intron_H3K27ac_processed.tsv.gz 3.5 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_SOX-MITF_combinations_enh-BC_list.tsv.gz 872.2 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_SOX-MITF_combinations_processed.tsv.gz 1.8 Kb (ftp)(http) TSV
GSE180879_CHEQ-seq_SOX10-KD_enh-BC_list.tsv.gz 839.9 Mb (ftp)(http) TSV
GSE180879_CHEQ-seq_SOX10-KD_processed.tsv.gz 217.2 Kb (ftp)(http) TSV
GSE180879_STARR-seq_ATAC_processed.tsv.gz 3.1 Kb (ftp)(http) TSV
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Processed data are available on Series record

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