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Series GSE121355 Query DataSets for GSE121355
Status Public on Aug 01, 2019
Title A pliable mediator acts as a functional, rather than an architectural bridge, between promoters and enhancers
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Our mechanistic understanding of Mediator derives largely from studies of the 25-subunit yeast complex. Here we combine CRISPR-Cas9 genetic screens, degron assays, in situ Hi-C, and cryo-EM to dissect the function and structure of the 33-subunit mammalian Mediator (mMED). Deletion analyses in B, T and ES cells reveal that depletion of the entire complex blocks PolII recruitment genome-wide, while loss of non-essential subunits, including the Tail module, primarily affects promoters linked to multiple enhancers. Contrary to current models, we find that mMED is not required to tether regulatory DNA, a topological activity controlled predominantly by architectural proteins. Structurally, we show that alterations in the Tail module, particularly at the core-Tail interphase, effect crucial mMED-PolII contacts, providing a rationale for how TFs stabilize the mMED-PolII holoenzyme and promote gene expression. Our studies therefore reveal key insights into how Mediator functionally bridge promoters and enhancers to regulate transcription initiation in higher eukaryotes.
Overall design ChIP-seq, ATACseq, Hi-C,PromterCaputre Hi-C, CRISPR screen and RNAseq from mouse ESC, CD4+ T cell or CH12 cell line and/or human HCT-116 cell line

The processed data files generated from multiple samples are indicated in the corresponding sample description field, and linked to the Series records or to the corresponding 'r1' sample records.
Contributor(s) Khattabi L, Zhao H, Kalchschmidt J, Young N, Jung S, van Blerkom P, Kieffer-Kwon P, Kieffer-Kwon K, Park S, Wang X, Krebs J, Tripathi S, Sakabe N, Sobreira DR, Huang S, Rao SS, Pruett N, Chauss D, Sadler E, Lopez A, Nobrega MA, Aiden EL, Asturias FJ, Casellas R
Citation(s) 31402173
Submission date Oct 16, 2018
Last update date Oct 31, 2019
Contact name Seolkyoung Jung
Organization name NIH
Department NIAMS
Lab biodata mining and discovery section
Street address 10 Center Dr
City bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (6)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16417 Illumina MiSeq (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (201)
GSM3432329 ch12_Ccncmm_mRNA_c1
GSM3432330 ch12_Ccncmm_mRNA_c2
GSM3432331 ch12_Ccncmm_mRNA_c3
BioProject PRJNA497125
SRA SRP165933

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
GSE121355_RAW.tar 50.3 Gb (http)(custom) TAR (of BEDGRAPH, BW, HIC, TXT)
GSE121355_ch12_Med14Nsmash_Hic_APR60h_inter.hic 5.0 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_inter_30.hic 4.6 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr1_inter.hic 1.3 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr1_inter_30.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr2_inter.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr2_inter_30.hic 1.1 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr3_inter.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr3_inter_30.hic 1.1 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr4_inter.hic 1.4 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr4_inter_30.hic 1.3 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr5_inter.hic 1.0 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr5_inter_30.hic 981.2 Mb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr6_inter.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr6_inter_30.hic 1.1 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr7_inter.hic 1.4 Gb (ftp)(http) HIC
GSE121355_ch12_Med14Nsmash_Hic_APR60h_tr7_inter_30.hic 1.3 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr1_inter.hic 3.5 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr1_inter_30.hic 3.2 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr2_inter.hic 3.9 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr2_inter_30.hic 3.6 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr3_inter.hic 4.3 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr3_inter_30.hic 4.0 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr4_inter.hic 4.1 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br1_tr4_inter_30.hic 3.8 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr1_inter.hic 2.8 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr1_inter_30.hic 2.6 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr2_inter.hic 2.5 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr2_inter_30.hic 2.3 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr3_inter.hic 2.6 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr3_inter_30.hic 2.4 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr4_inter.hic 4.2 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_br2_tr4_inter_30.hic 3.8 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_inter.hic 14.9 Gb (ftp)(http) HIC
GSE121355_ch12_Tailless_Hic_inter_30.hic 13.7 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_inter.hic 17.8 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_inter_30.hic 16.5 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr1_inter.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr1_inter_30.hic 1.1 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr2_inter.hic 1.3 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr2_inter_30.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr3_inter.hic 1.0 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr3_inter_30.hic 965.9 Mb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr4_inter.hic 1020.0 Mb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr4_inter_30.hic 942.3 Mb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr5_inter.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr5_inter_30.hic 1.1 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr6_inter.hic 1.2 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr6_inter_30.hic 1.1 Gb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr7_inter.hic 43.5 Mb (ftp)(http) HIC
GSE121355_ch12_wt_Hic_APR60h_tr7_inter_30.hic 42.1 Mb (ftp)(http) HIC
GSE121355_esc_Cscreen_res.txt.gz 20.7 Kb (ftp)(http) TXT
GSE121355_hct116_Rad21DegronPolIIhet_HiC_amanitin_inter30.hic 4.2 Gb (ftp)(http) HIC
GSE121355_hct116_Rad21DegronPolIIhet_HiC_auxinamanitin_inter30.hic 5.2 Gb (ftp)(http) HIC
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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