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Set1 and MLL1/2 target distinct sets of functionally different genomic loci in vivo: An in depth ChIP-seq analysis of H3K4me3 targets in vivo and upon Set1 and mll1 knockdown

ABSTRACT: Histone H3 lysine 4 trimethylation (H3K4me3) is known to correlate with both active and poised genomic loci, yet many questions remain regarding its functional roles in vivo. We identify functional genomic targets of two H3K4 methyltransferases, Set1 and MLL1/2, in both the stem cells (X1) and differentiated tissue (Xins) of the planarian flatworm Schmidtea mediterranea. We show that, despite their common substrate, these enzymes target distinct genomic loci in vivo, which are distinguishable by the footprint each enzyme leaves on the chromatin template, i.e., the breadth of the H3K4me3 peak. Whereas Set1 targets are broadly associated with the maintenance of the stem cell population, MLL1/2 targets are specifically enriched for genes involved in ciliogenesis. These data not only confirm that chromatin regulation is fundamental to planarian stem cell function, but also provide evidence for post-embryonic functional specificity of H3K4me3 methyltransferases in vivo. To test this, we looked at the H3K4me3 chromatin profile in WW, X1 and Xins cell types upon knockdown of set1, mll1/2, as well as WT. Examine differential binding of H3K4me3 in different experimental conditions. The experiment performed yielded a total of 58 samples.

ORGANISM(S): Schmidtea mediterranea

SUBMITTER: Alex Chitsazan

PROVIDER: E-GEOD-74153 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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H3K36me3 is significantly more enriched at Set1-affected loci than at MLL1/2-affected loci in planarian stem cells

Project description:Histone H3 lysine 4 trimethylation (H3K4me3) is known to correlate with both active and poised genomic loci, yet many questions remain regarding its functional roles in vivo. We identify functional genomic targets of two H3K4 methyltransferases, Set1 and MLL1/2, in both the stem cells (X1) and differentiated tissue (Xins) of the planarian flatworm Schmidtea mediterranea. We show that, despite their common substrate, these enzymes target distinct genomic loci in vivo, which are distinguishable by the footprint each enzyme leaves on the chromatin template, i.e., the breadth of the H3K4me3 peak. Whereas Set1 targets are broadly associated with the maintenance of the stem cell population, MLL1/2 targets are specifically enriched for genes involved in ciliogenesis. These data not only confirm that chromatin regulation is fundamental to planarian stem cell function, but also provide evidence for post-embryonic functional specificity of H3K4me3 methyltransferases in vivo. To test this, we looked at the H3K4me3 chromatin profile in WW, X1 and Xins cell types upon knockdown of set1, mll1/2, as well as WT. Examine binding of H3K36me3 in WT in Planarian. The experiment performed yielded a total of 2 samples. These samples validate the main ChIP samples.

2015-12-17 | E-GEOD-74419 | biostudies-arrayexpress

Set1 and MLL1/2 target distinct sets of functionally different genomic loci in vivo: An in depth ChIP-seq analysis of H3K4me3 targets in vivo and upon Set1 and mll1 knockdown

2015-12-17 | GSE74153 | GEO

H3K36me3 is significantly more enriched at Set1-affected loci than at MLL1/2-affected loci in planarian stem cells

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Set1 and MLL1/2 target distinct sets of functionally different genomic loci in vivo: An in depth RNA-seq analysis of H3K4me3 targets in vivo and upon Set1 and mll1 knockdown

Project description:This study identifies expression differences upon knockdown of two H3K4 methyltransferases, Set1 and MLL1/2, in both the stem cells (X1) and whole worm (WW) tissue of the planarian flatworm Schmidtea mediterranea. To test this, we looked at the RNA-seq expression profile in WW and X1 tissue types upon RNAi knockdown of set1, mll1/2 and compared to a non-targeted RNAi control, unc22.

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Conserved functional antagonism between CELF and MBNL proteins regulates stem cell-specific alternative splicing and regeneration in planarians (dataset 2)

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Single-cell analysis reveals prominent classes within the planarian stem cell compartment

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Cla4 catalyzed Set1 phosphorylation

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2023-10-24 | PXD042010 | Pride

RNA Seq analysis of sorted Schmidtea mediterranea X1 and Xins cells to identify factors specific to neoblasts

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2015-12-17 | E-GEOD-73027 | biostudies-arrayexpress

Expression analysis on Mll1+/+ and Mll1-/- MEFs

Project description:Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II A common landmark of activated genes is the presence of trimethylation on lysine 4 of histone H3 (H3K4) at promoter regions. The Set1/COMPASS was the founding member and the only H3K4 methylases in S. cerevisiae, however, in mammals at least six H3K4 methylases Set1A/B and MLL1-4 are found in COMPASS-like complexes capable of methylating H3K4. To gain further insight into the different roles and functional targets for the H3K4 methylases, we have undertaken a genome-wide analysis of H3K4 methylation pattern in wild-type Mll1+/+ and Mll1-/- mouse fibroblasts (MEFs). We found that Mll1 is required for the H3K4 trimethylation of less than 5% of promoters carrying this modification. Many of these genes, which include developmental regulators such as Hox genes show decreased levels of RNA polymerase II recruitment and expression concomitant with the loss of H3K4 methylation. Although Mll1 is only required for the methylation of a subset of Hox genes, Menin, a component of the Mll1 and Mll2 complexes, is required for the overwhelming majority of H3K4 methylation at Hox loci. However, the loss of MLL3/4 and/or the Set1 complexes have little to no effect on the Hox loci H3K4 methylation or expression levels in these MEFs. Together these data provide insight into redundancy and specialization of COMPASS-like complexes in mammals and provide evidence on a possible role for Mll1-mediated H3K4 methylation in the regulation of transcriptional initiation. Expression arrays were done with Mll1+/+ and Mll1-/- mouse embryonic fibroblasts. Four replicates were done (dyes were swapped). DNA was hybridized to Agilent Mouse Whole Genome Expression Arrays (4x44k).

2009-10-20 | E-GEOD-18261 | biostudies-arrayexpress

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