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Series GSE199431 Query DataSets for GSE199431
Status Public on Apr 26, 2024
Title Position-dependent function of human sequence-specific transcription factors
Organisms Homo sapiens; Mus musculus; Chlorocebus sabaeus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Patterns of transcriptional activity are encoded in our genome through regulatory elements such as promoters or enhancers that, paradoxically, often contain similar assortments of sequence-specific transcription factor (TF) binding sites. Knowledge of how these sequence motifs encode multiple, often overlapping gene expression programs is central to understanding gene regulation and how mutations in non-coding DNA manifest in disease. Exploiting natural genetic variation, perturbation of endogenous TF protein levels, and analysis of synthetic regulatory elements using a novel transcription start site (TSS) capturing massively parallel reporter assay approach, here we show that the outcome of TF binding on transcription initiation is position dependent. Analyzing TF motif occurrences relative to the TSS, we identified several motifs with highly preferential and superhelical positioning. We show that these patterns are a combination of a TF's distinct functional profiles: many TFs, including canonical activators like NRF1, NFY, Sp1 or YY1, activate or repress transcription initiation depending on their precise position relative to the TSS. As such, TFs can collectively guide the site and frequency of transcription initiation. More broadly, these findings reveal how similar assortments of TFs, but with different spatial relationships, can result in distinct gene regulatory outcomes and underscore a critical role for TSS data in decoding the regulatory information of our genome.
Overall design Profiling transcription initiation in the genome using csRNA-seq or from massively parallel reporter assays using TSS-MPRA, stable RNA levels by RNA-seq, TF occupany by ChIP-seq.
Contributor(s) Duttke SH, Guzman C, Chang M, Xie J, Delos Santos NP, Carlin AF, Heinz S, Benner C
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Submission date Mar 25, 2022
Last update date Apr 27, 2024
Contact name Christopher Benner
Organization name University of California, San Diego (UCSD)
Department Medicine
Street address 9500 Gilman Dr. MC 0640
City La Jolla
State/province California
ZIP/Postal code 92093-0640
Country USA
Platforms (4)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (56)
GSM5972708 U2OS csRNA-seq GFP(Ctrl) siRNA rep1
GSM5972709 U2OS csRNAinput-seq GFP(Ctrl) siRNA rep1
GSM5972710 U2OS csRNA-seq GFP(Ctrl) siRNA rep2
BioProject PRJNA819990

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
GSE199431_RAW.tar 910.0 Kb (http)(custom) TAR (of BED, TSV)
GSE199431_TFmutation.fa.gz 34.2 Kb (ftp)(http) FA
GSE199431_TFposScreen-r1.tssLevels.tsv.gz 212.7 Kb (ftp)(http) TSV
GSE199431_TFposScreen-r2.tssLevels.tsv.gz 213.6 Kb (ftp)(http) TSV
GSE199431_TFposScreen.fa.gz 25.5 Kb (ftp)(http) FA
GSE199431_TFposSweep-r1.tssLevels.tsv.gz 212.7 Kb (ftp)(http) TSV
GSE199431_TFposSweep-r2.tssLevels.tsv.gz 213.6 Kb (ftp)(http) TSV
GSE199431_TFposSweep.fa.gz 25.9 Kb (ftp)(http) FA
GSE199431_fpkm.txt.gz 1.3 Mb (ftp)(http) TXT
GSE199431_peaks.U2OS.dnNRF1.HA.bed.gz 360.5 Kb (ftp)(http) BED
GSE199431_tss.BMDM.SpretVsC57Bl6.KLA.bed.gz 4.0 Mb (ftp)(http) BED
GSE199431_tss.BMDM.SpretVsC57Bl6.notx.bed.gz 4.4 Mb (ftp)(http) BED
GSE199431_tss.HEK293T.bed.gz 3.5 Mb (ftp)(http) BED
GSE199431_tss.HepG2.bed.gz 2.8 Mb (ftp)(http) BED
GSE199431_tss.U2OS.dnNRF1vsEGFP.bed.gz 2.1 Mb (ftp)(http) BED
GSE199431_tss.U2OS.siGFP.bed.gz 1.6 Mb (ftp)(http) BED
GSE199431_tss.U2OS.siNRF1vsGFP.bed.gz 2.5 Mb (ftp)(http) BED
GSE199431_tss.U2OS.siYY1vsGFP.bed.gz 2.5 Mb (ftp)(http) BED
GSE199431_tss.Vero.bed.gz 2.1 Mb (ftp)(http) BED
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Raw data are available in SRA
Processed data are available on Series record

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