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Series GSE133760 Query DataSets for GSE133760
Status Public on Jul 03, 2022
Title Hierarchical enhancers 1 confer the temporal and partially compensatory transcriptional regulation of Nkx2-5 during heart development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary We comprehensively interrogate enhancers U1 and U2 in controlling Nkx2-5 transcription during heart development. Serial genomic deletions in mice reveal a functional hierarchy of U1 and U2 as evidenced by stage-dependent phenotypic variations. Specifically, U1 and U2 function redundantly to confer Nkx2-5 expression at early stages, but U2 instead of U1 supported its expression at later stages of heart chamber formation and maturation. Combined deletions markedly reduce Nkx2-5 dosage as early as E7.5, despite being largely reinstated two days later, displaying heart malformations with precocious differentiation of cardiac progenitors. Together, we propose a model that the temporal and partially compensatory regulatory function of two enhancers dictates a TF?s dosage and specificity during development.
Overall design 1) H3K27ac ChIP-seq and ATAC-seq data on E16.5 ventricles from Control and U2KO mice. DKO mice were generated by deleting both U1 and U2 locus and U2KO mice were generated by deleting only U2 locus using CRISPR-Cas9 genome editing. 2) Single cells of outflow tract (OFT) or heart tube (HT) were derived for scRNA-seq from DKO and Control mice at E8.25. 3) H3K27ac ChIP-seq data on E9.5 hearts from Control and DKO mice. 4) NKX2-5 ChIP-seq data on E9.5 hearts from DKO mice. 5) Hi-C with WT and U1U2-DKO E8.5 mouse hearts.
Contributor(s) Li CC, Zhang J, Liu Y, Wang Q, Xiong H, Li X, He A, Ai S
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Submission date Jul 03, 2019
Last update date Mar 31, 2023
Contact name Yaxi Liu
Phone 86-18813039296
Organization name Peking University
Street address 5 Yiheyuan Road
City Beijing
ZIP/Postal code 100871
Country China
Platforms (2)
GPL21273 HiSeq X Ten (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (37)
GSM3926917 IgG, E9.5 heart, Control
GSM3926918 H3K27ac, E9.5 heart, Control, rep1
GSM3926919 H3K27ac, E9.5 heart, Control, rep2
BioProject PRJNA552476
SRA SRP212875

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
GSE133760_96_8bp_barcode.txt.gz 669 b (ftp)(http) TXT
GSE133760_RAW.tar 24.3 Gb (http)(custom) TAR (of BW, COOL, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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