NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE95374 Query DataSets for GSE95374
Status Public on Dec 06, 2017
Title Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators
Organisms Homo sapiens; Mus musculus
Experiment type Other
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Transposable elements (TEs) are now recognized not only as parasitic DNA, whose spread in the genome must be controlled by the host, but also as major players in shaping genome evolution and providing genetic substrates for evolving new regulatory functions. Long INterspersed Element-1 (LINE-1 or L1), the only currently autonomous mobile transposon in humans, occupies 17% of the genome and continues to generate inter- and intra-individual genetic variation, in some cases resulting in disease. Nonetheless, our knowledge of how L1 activity is controlled and what function L1s play in host gene regulation remains fragmentary. Here, we use CRISPR/Cas9 screening strategies in two distinct human cell lines to provide the first genome-wide survey of genes involved in L1 retrotransposition control. Through this approach we identified functionally diverse genes that either promote or restrict L1 retrotransposition. These factors control the L1 life cycle at transcriptional or post-transcriptional levels, and in a manner which in some, but not in other cases depends on the endogenous L1 sequence, underscoring the complexity of L1 regulation. We further investigated L1 restriction by three candidate regulators, MORC2 and HUSH (human silencing hub) complex subunits TASOR and MPP8. HUSH/MORC2 selectively bind evolutionarily young, full-length L1s immersed within transcriptionally permissive euchromatic environment, and promote H3K9me3 deposition for transcriptional silencing. Interestingly, these silencing events often occur within introns of transcriptionally active host genes, and lead to down-regulation of host gene expression in a HUSH/MORC2-dependent manner. Together, our data provide a rich resource for studies of L1 retrotransposition, elucidate a novel L1 restriction pathway, and illustrate how epigenetic silencing of TEs can influence host gene expression programs.
 
Overall design Identify L1 regulators by one genome-wide CRISPR screen followed by one secondary batch screen in K562 and HeLa cells; Identify the binding profiles of MORC2, MPP8 and TASOR by ChIP-seq in wild type and KO cells; Identify the H3K9me3 methylation changes and RNA polymerase II binding site changes by ChIP-seq and the transcriptional changes by polyA-selected RNA-seq in wild-type and corresponding KO cells.
 
Contributor(s) Nian L, Cameron L, Tomek S, Edward G, Michael B, Joanna W
Citation(s) 29211708
Submission date Feb 25, 2017
Last update date Jul 25, 2021
Contact name Nian Liu
E-mail(s) liunian88@gmail.com
Organization name Stanford University
Department Chemical and Systems Biology
Lab Wysocka lab
Street address 265 Campus Drive, Rm. G3145
City Palo Alto
State/province CA
ZIP/Postal code 94306
Country USA
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (104)
GSM2509447 Genome-wide-screen_untreated_rep1
GSM2509448 Genome-wide-screen_untreated_rep2
GSM2509449 Genome-wide-screen_G418_rep1
Relations
BioProject PRJNA376803
SRA SRP100725

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
GSE95374_Batch_screen_results.txt.gz 31.2 Kb (ftp)(http) TXT
GSE95374_Genome_wide_screen_results.txt.gz 1.9 Mb (ftp)(http) TXT
GSE95374_HeLa_Genome_wide_screen.txt.gz 1.9 Mb (ftp)(http) TXT
GSE95374_HeLa_secondary_screen.txt.gz 31.0 Kb (ftp)(http) TXT
GSE95374_K562__opt_-L1-G418_secondary_screen.txt.gz 30.2 Kb (ftp)(http) TXT
GSE95374_RAW.tar 27.3 Gb (http)(custom) TAR (of BW)
GSE95374_WT1_CHIP_K9me3.bw 580.7 Mb (ftp)(http) BW
GSE95374_WT2_CHIP_K9me3.bw 524.0 Mb (ftp)(http) BW
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap