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GEO Series: GSE92366

Title: H3K4 Methylation-Mediated Memory of an Active Transcriptional State Impairs Nuclear Reprogramming

Summary

Xenopus eggs can induce the reversal of differentiation processes of somatic cells. Yet, the egg is not fully efficient in reprogramming a differentiated nucleus, as certain genes retain a memory of gene expression of their somatic cell of origin. This is thought to be a reason for the low success rate of current cloning and reprogramming strategies. While previous studies addressed extensively the mechanisms that maintain an inactive state of genes (OFF-memory), we investigated the importance of memory of an active transcriptional state (ON-memory) in maintaining cell fate identity and on resistance to reprogramming. We find that donor cell-type specific ON-memory gene-expression in the wrong cell-type of nuclear transfer (NT)-embryos is as common as OFF-memory gene-expression. When compared to properly reprogrammed genes, we find that ON-memory genes show an elevated level of the active histone mark H3K4me3 in endoderm donor cells. Importantly, we show that a reduction of H3K4 methylation level in donor cells decreases the extent of ON-memory gene expression, globally improves transcriptional reprogramming, and enhances the development of NT-embryos. Therefore, our study reveals that H3K4 methylation safeguards endoderm cell identity and acts as a major barrier for efficient reprogramming in NT-embryos. Furthermore, our results suggest that efficient cell fate reprogramming not only relies on the erasure of epigenetic modifications conferring OFF-memory but also crucially depends on the removal of H3 lysine 4 methylation-mediated memory of an active state of gene expression.


Contributors: Angela Simeone, Eva Hörmanseder, George Allen, Charles Bradshaw, Magdalena Figlmüller, Jerome Jullien, John Gurdon

Experiment Type: 73 samples, single-ended RNA-seq libraries from neurula stage 18 or 21 endoderm and gastrula stage 11 ectoderm samples; 2 single-ended ChIP-seq libraries from endoderm cells of neurula (stage 21) embryos with antibody for H3K4me3, 2 replicates for each histone modification pull-down.

Experiment Reagents: h3-3a.L, Tg(h3-3a.LK4M), Tg(Mmu.kdm5bdel),

Article: XB-ART-54691, PubMed

Source: NCBI GEO, Xenbase FTP

Samples: (DEG = Differentially Expressed Genes; GSM = GEO Sample Number)
Sample View GSMs Assay Type
ectoderm - NF11 GSM2428183  GSM2428184  GSM2428185  GSM2428186  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell - NF11 DEG GSM2428187  GSM2428188  GSM2428189  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
ectoderm - NF11 GSM2428212  GSM2428213  GSM2428214  GSM2428215  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell + Mmu.kdm5bH499A_del - NF11 DEG GSM2428216  GSM2428217  GSM2428218  GSM2428219  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
mRNA injection Tg(Mmu.kdm5bH499A_del) kdm5b (Xla) NF stage 18 endodermal cell
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell + Mmu.kdm5bdel - NF11 DEG GSM2428220  GSM2428221  GSM2428222  GSM2428223  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
mRNA injection Tg(Mmu.kdm5bdel) kdm5b (Xla) NF stage 18 endodermal cell
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
ectoderm - NF11 GSM2428243  GSM2428244  GSM2428245  GSM2428246  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell + h3-3a.L - NF11 DEG GSM2428247  GSM2428248  GSM2428249  GSM2428250  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
mRNA injection   h3-3a.L NF stage 21 endodermal cell
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell + h3-3a.LK4M - NF11 DEG GSM2428251  GSM2428252  GSM2428253  GSM2428254  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
mRNA injection Tg(h3-3a.LK4M) h3-3a.L NF stage 21 endodermal cell
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
ectoderm - NF11 GSM2428200  GSM2428201  GSM2428202  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell - NF11 DEG GSM2428203  GSM2428204  GSM2428205  GSM2428206  GSM2428207  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
ectoderm - NF11 GSM2428191  GSM2428192  GSM2428193  GSM2428194  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell - NF11 DEG GSM2428195  GSM2428196  GSM2428197  GSM2428198  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
ectoderm - NF11 GSM2428228  GSM2428229  GSM2428230  GSM2428231  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell + Mmu.kdm5bH499A_del - NF11 DEG GSM2428232  GSM2428233  GSM2428234  GSM2428235  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
mRNA injection Tg(Mmu.kdm5bH499A_del) kdm5b (Xla) NF stage 18 endodermal cell
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
   ectoderm + SCNT endoderm cell + Mmu.kdm5bdel - NF11 DEG GSM2428236  GSM2428237  GSM2428238  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
SCNT   mature egg stage egg
mRNA injection Tg(Mmu.kdm5bdel) kdm5b (Xla) NF stage 18 endodermal cell
Conditions:
Tissue Assay Stages ChIP Antibody
ectoderm NF stage 11  
endoderm + h3-3a.L - NF21 GSM2428239  GSM2428240  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
mRNA injection h3-3a.L h3-3a.L NF stage 1 zygote
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 21  
   endoderm + h3-3a.LK4M - NF21 DEG GSM2428241  GSM2428242  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
mRNA injection Tg(h3-3a.LK4M) h3-3a.L NF stage 1 zygote
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 21  
endoderm + Mmu.kdm5bdel - NF18 GSM2428210  GSM2428211  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
mRNA injection Tg(Mmu.kdm5bdel) kdm5b (Xla) NF stage 1 zygote
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18  
   endoderm + Mmu.kdm5bH499A_del - NF18 DEG GSM2428208  GSM2428209  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
mRNA injection Tg(Mmu.kdm5bH499A_del) kdm5b (Xla) NF stage 1 zygote
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18  
endoderm + Mmu.kdm5bdel - NF18 GSM2428226  GSM2428227  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
mRNA injection Tg(Mmu.kdm5bdel) kdm5b (Xla) NF stage 1 zygote
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18  
   endoderm + Mmu.kdm5bH499A_del - NF18 DEG GSM2428224  GSM2428225  RNA-Seq
Background: Xla.pigmentedNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
mRNA injection Tg(Mmu.kdm5bH499A_del) kdm5b (Xla) NF stage 1 zygote
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18  
input endoderm - NF18 GSM2428256  ChIP-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18 to NF stage 21  
   H3K4me3 endoderm - NF18 GSM2428255  ChIP-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18 to NF stage 21 Tri-Methyl H3f3a Ab19
input endoderm - NF18 GSM2428258  ChIP-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18 to NF stage 21  
   H3K4me3 endoderm - NF18 GSM2428257  ChIP-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 18 to NF stage 21 Tri-Methyl H3f3a Ab19
endoderm - NF21 GSM2428182  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 21  
endoderm - NF21 GSM2428190  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 21  
endoderm - NF21 GSM2428199  RNA-Seq
Background: Xla.pigmentedNasco
Conditions:
Tissue Assay Stages ChIP Antibody
endoderm NF stage 21  
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