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Series GSE103076 Query DataSets for GSE103076
Status Public on Dec 31, 2022
Title Structural and Genome-wide Analysis Support a Role for SETMAR in Transcriptional Regulation
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Approximately 50 million years ago, the Hsmar1 transposon entered the primate lineage giving rise to a new protein, a chimeric fusion of a SET domain and the Hsmar1 transposase. This protein, SETMAR or Metnase, is broadly expressed in human tissues and has been shown to retain its ancestral sequence-specific binding to Hsmar1 terminal inverted repeat (TIR) sequences found at the ends of the transposons. Despite the fact that there were estimated to be anywhere from 1500-7000 TIR sites within the human genome, the relevance of SETMAR-TIR interactions was unknown. Here, we report the crystal structure of the SETMAR DNA-binding domain (DBD) complexed with TIR DNA at 2.37 Å. The DBD structure includes two helix-turn-helix motifs (HTH1 and HTH2), which dimerize through HTH1, and confer sequence-specific recognition of the TIR through nucleobase-specific interactions with R371 in HTH1 and R417, H427, S428, and R432 in HTH2. The extent of genome-wide binding was determined by chromatin immunoprecipitation sequencing (ChIP-seq) analysis yielding a total of 7457 SETMAR bound sites. The effect of SETMAR on the transcriptome was assessed by RNA-seq analysis; among the 177 differentially regulated transcripts, a cluster of histones on chromosome 6 were found to be repressed. The dimeric SETMAR structure with each DBD bound to TIR DNA, the presence of eleven TIR sites within the histone gene cluster, and previously reported DNA looping activity are consistent with a direct regulatory mechanism in which SETMAR represses mRNA expression for specific genes through chromatin looping.
 
Overall design HEK293T cells were transfected with either empty vector or vector containing full length wild type SETMAR gene and differential gene expression was determined by Next Gen RNA sequencing
 
Contributor(s) Georgiadis M, Bates A
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Submission date Aug 24, 2017
Last update date Dec 31, 2022
Contact name Millie Georgiadis
E-mail(s) mgeorgia@iu.edu
Organization name Indiana University School of Medicine
Department Biochemistry and Molecular Biology
Lab Dr. Millie Georgiadis
Street address 635 Barnhill Drive
City Indianapolis
State/province Indiana
ZIP/Postal code 46202
Country USA
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (8)
GSM2753383 Void 1
GSM2753384 Void 2
GSM2753385 Void 3
Relations
BioProject PRJNA400164
SRA SRP116225

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE103076_Georgiadis_RNAseq_STAR_featureCounts_edgeR_20170418_WTvsVoid.xlsx 5.7 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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