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Series GSE180175 Query DataSets for GSE180175
Status Public on Oct 02, 2022
Title Hi-TrAC reveals fine-scale chromatin structures organized by transcription factors
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Summary The three-dimensional genomic structure plays a critical role in gene expression, cellular differentiation, and pathological conditions. Previous studies have extensively investigated the structures including A/B compartments and topologically associating domains (TADs) at a scale from hundreds of kilobases (kb) to megabases (Mb). However, fine-scale chromatin architectures, particularly enhancer-promoter interactions, which are often within 100 kb and critical for the temporospatial regulation of expression, remain to be fully characterized due to technical limitations. In this study, we report Hi-TrAC as a proximity ligation free, robust, and sensitive technique to profile genome-wide chromatin interactions at high-resolution among accessible regulatory elements. Hi-TrAC detects chromatin looping among accessible chromatin regions at single nucleosome resolution. We observed that cell-specifically expressed genes are harbored in active sub-TADs. With almost half million identified loops, we constructed a comprehensive interaction network of regulatory elements across the genome. After integrating chromatin binding profiles of transcription factors (TFs), we discovered that cohesin complex and CTCF are responsible for organizing long-range chromatin loops, which are related with domain formation, whereas ZNF143 and HCFC1 are involved in structuring short-range chromatin loops between regulatory elements, which directly regulate gene expression. Thus, here we developed a new methodology to identify a delicate and comprehensive network of cis regulatory elements, revealing the complexity and a division of labor of TFs in chromatin looping for genome organization and gene expression.
 
Overall design The genome structure of GM12878, K562 and mESC cells was studied by a newly developed technique Hi-TrAC. Chromatin binding profiles of architectural proteins CTCF, RAD21, HCFC1 and ZNF143 were studied by ChIP-seq. The effect of these four proteins on gene expression was investigated by RNA-seq, accessbility changes were studied by ATAC-seq, changes of chromatin interactions were also validated by Hi-C.
 
Contributor(s) Liu S, Cao Y, Cui K, Tang Q, Zhao K
Citation(s) 36335136
Submission date Jul 15, 2021
Last update date Nov 21, 2022
Contact name Yaqiang Cao
E-mail(s) caoyaqiang0410@gmail.com
Organization name NHLBI
Department System Biology Center
Lab Laboratory of Epigenome Biology
Street address 9000 Rockville Pike
City Bethesda
State/province Maryland
ZIP/Postal code 20892
Country USA
 
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (136)
GSM5454673 Hi-TrAC_GC1477_1496_2248_GM12878_bio1_tech1
GSM5454674 Hi-TrAC_GC1478_1497_2249_GM12878_bio1_tech2
GSM5454675 Hi-TrAC_GC1479_1498_2250_GM12878_bio1_tech3
Relations
BioProject PRJNA746963
SRA SRP328503

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
GSE180175_K562_cas9.txt.gz 1.2 Mb (ftp)(http) TXT
GSE180175_RAW.tar 51.3 Gb (http)(custom) TAR (of BEDPE, BW)
GSE180175_RNA-seq_Exp_K562_4TFs_KD.txt.gz 2.2 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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