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Series GSE155229 Query DataSets for GSE155229
Status Public on Jul 24, 2023
Title Genome-wide analysis of enhancers repressed by Nkx2.2 in spinal motor neuron progenitors
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Unambiguous consolidation of cell identity relies on transcription factors (TFs) acting to suppress alternative lineages, yet few general principles have emerged explaining how repressors manipulate chromatin landscapes to achieve stable gene silencing, especially in instances when these TFs are only temporarily activated. The TF Nkx2.2 is transiently expressed in CNS progenitors yet permanently abrogates somatic motor neuron (sMN) differentiation via interactions with Groucho (Grg) co-repressors. We show that Nkx2.2 inhibits regulatory elements of progenitor and postmitotic sMN transcripts by utilizing Grg to evict co-activators. Surprisingly, co-activator eviction was accomplished using Grg proteins already present at enhancers, rather than through the additional recruitment of Grg or other co-repressors. Nkx2.2-mediated enhancer silencing also led to the loss of H3K27ac modifications from H3K27me3+H3K27ac+ proximal promoters of key sMN genes, facilitating persistent repression of the sMN progenitor program after Nkx2.2 downregulation. These results imply that active loci are poised for suppression, and repressor binding mediates the transition through co-activator displacement.
Overall design Examination of ChIP-seq profiles of 2 transcription factors (TFs), 3 histone modifications, 4 TF cofactors, and total RNA profiles during the differentiation of mouse ES cell-derived spinal motor neuron progenitors expressing a wildtype copy of Nkx2.2 tagged by FLAG under the control of a doxycycline (DOX) inducible promotor (iNkx2.2), a TN-domain mutant copy of Nkx2.2 tagged by FLAG under the control of a doxycycline (DOX) inducible promotor (iTNmut), or no Nkx2.2 (pMN). Replicates are provided for all ChIP-seq samples except Sox2, Med1, and H3K27me3; an input sample is also provided. RNA samples are provided in triplicates.
Contributor(s) Abarinov EV, Closser M, Guo Y, Guo X, Chalkey M, Gifford DK, Mazzoni EO, Sussel L, Wichterle H
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Submission date Jul 27, 2020
Last update date Jul 24, 2023
Contact name Elena Abarinov
Organization name University of Colorado at Denver
Street address 1775 Aurora Ct
City Aurora
State/province Colorado
ZIP/Postal code 80045
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (56)
GSM4697739 RNA-seq pMN day4 progenitors rep1
GSM4697740 RNA-seq pMN day4 progenitors rep2
GSM4697741 RNA-seq pMN day4 progenitors rep3
BioProject PRJNA648995
SRA SRP273778

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
GSE155229_Grg_GEM_events.txt.gz 9.4 Mb (ftp)(http) TXT
GSE155229_Grg_logCPM.txt.gz 512.4 Kb (ftp)(http) TXT
GSE155229_H3K27ac_day4_logCPM.txt.gz 441.0 Kb (ftp)(http) TXT
GSE155229_H3K27ac_sMN_day6_logCPM.txt.gz 194.5 Kb (ftp)(http) TXT
GSE155229_H3K27me3_logCPM.txt.gz 64.9 Kb (ftp)(http) TXT
GSE155229_H3K4me1_logCPM.txt.gz 929.5 Kb (ftp)(http) TXT
GSE155229_HDAC2_logCPM.txt.gz 293.0 Kb (ftp)(http) TXT
GSE155229_Med1_logCPM.txt.gz 270.9 Kb (ftp)(http) TXT
GSE155229_Nkx2.2-Flag_GEM_events.txt.gz 9.4 Mb (ftp)(http) TXT
GSE155229_Nkx2.2_logCPM.txt.gz 378.9 Kb (ftp)(http) TXT
GSE155229_RAW.tar 20.0 Mb (http)(custom) TAR (of TXT)
GSE155229_RNAseq_FPKM.txt.gz 832.7 Kb (ftp)(http) TXT
GSE155229_RNAseq_SigGenes.txt.gz 728.3 Kb (ftp)(http) TXT
GSE155229_RNAseq_readcounts.txt.gz 474.9 Kb (ftp)(http) TXT
GSE155229_RawCounts_Grg.txt.gz 299.5 Kb (ftp)(http) TXT
GSE155229_RawCounts_H3K27me3.txt.gz 89.0 Kb (ftp)(http) TXT
GSE155229_RawCounts_H3K4me1.txt.gz 1.0 Mb (ftp)(http) TXT
GSE155229_RawCounts_HDAC2.txt.gz 333.9 Kb (ftp)(http) TXT
GSE155229_RawCounts_Med1.txt.gz 185.0 Kb (ftp)(http) TXT
GSE155229_RawCounts_Nkx2.2-Flag.txt.gz 243.5 Kb (ftp)(http) TXT
GSE155229_RawCounts_Sox2.txt.gz 158.6 Kb (ftp)(http) TXT
GSE155229_RawCounts_day4_H3K27ac.txt.gz 426.1 Kb (ftp)(http) TXT
GSE155229_RawCounts_p300.txt.gz 372.1 Kb (ftp)(http) TXT
GSE155229_RawCounts_sMN_H3K27ac.txt.gz 298.7 Kb (ftp)(http) TXT
GSE155229_SigHDAC2.txt.gz 541.2 Kb (ftp)(http) TXT
GSE155229_Sig_Grg.txt.gz 1.5 Mb (ftp)(http) TXT
GSE155229_Sig_H3K27ac_day4.txt.gz 630.3 Kb (ftp)(http) TXT
GSE155229_Sig_H3K4me1.txt.gz 1.5 Mb (ftp)(http) TXT
GSE155229_Sig_Nkx2.2.txt.gz 763.4 Kb (ftp)(http) TXT
GSE155229_Sig_p300.txt.gz 2.1 Mb (ftp)(http) TXT
GSE155229_Sox2_GEM_events.txt.gz 1.3 Mb (ftp)(http) TXT
GSE155229_Sox2_logCPM.txt.gz 224.6 Kb (ftp)(http) TXT
GSE155229_p300_GEM_events.txt.gz 5.1 Mb (ftp)(http) TXT
GSE155229_p300_logCPM.txt.gz 598.9 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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