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PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells.

eLife | 2019

The PLZF transcription factor is essential for osteogenic differentiation of hMSCs; however, its regulation and molecular function during this process is not fully understood. Here, we revealed that the ZBTB16 locus encoding PLZF, is repressed by Polycomb (PcG) and H3K27me3 in naive hMSCs. At the pre-osteoblast stage of differentiation, the locus lost PcG binding and H3K27me3, gained JMJD3 recruitment, and H3K27ac resulting in high expression of PLZF. Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. The increased expression of NNMT correlated with a decline in SAM levels, which is dependent on PLZF and is required for osteogenic differentiation.

Pubmed ID: 30672466 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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MEME Suite - Motif-based sequence analysis tools (tool)

RRID:SCR_001783

Suite of motif-based sequence analysis tools to discover motifs using MEME, DREME (DNA only) or GLAM2 on groups of related DNA or protein sequences; search sequence databases with motifs using MAST, FIMO, MCAST or GLAM2SCAN; compare a motif to all motifs in a database of motifs; associate motifs with Gene Ontology terms via their putative target genes, and analyze motif enrichment using SpaMo or CentriMo. Source code, binaries and a web server are freely available for noncommercial use.

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Bowtie (tool)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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HEK293-FT (tool)

RRID:CVCL_6911

Cell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)

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MED12 Antibody (antibody)

RRID:AB_669756

This unknown targets MED12

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CRSP1/TRAP220 Antibody (antibody)

RRID:AB_577241

This unknown targets CRSP1/TRAP220

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Anti-JMJD3 (KDM6B) (antibody)

RRID:AB_2755046

This polyclonal targets JMJD3 (KDM6B)

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H3K4me1-human (antibody)

RRID:AB_10695148

This unknown targets H3K4me1

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EP300-human (antibody)

RRID:AB_2231120

This unknown targets EP300

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H3K36me3-human (antibody)

RRID:AB_1950412

This unknown targets H3K36me3

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Pol II (H-224) (antibody)

RRID:AB_2268548

This polyclonal targets POLR2A

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SUZ12-human (antibody)

RRID:AB_2196850

This monoclonal targets SUZ12

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H3K4me3-human (antibody)

RRID:AB_2616028

This monoclonal targets H3K4me3

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H3K27me3-human (antibody)

RRID:AB_2616029

This unknown targets H3K27me3

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Anti-RNF2 (RING1B) (antibody)

RRID:AB_2755047

This polyclonal targets RNF2 (RING1B)

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p130 (C-20) (antibody)

RRID:AB_632093

This polyclonal targets RBL2

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H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

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PLZF (H-300) (antibody)

RRID:AB_2304760

This polyclonal targets PLZF (H-300)

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GAPDH antibody [6C5] (antibody)

RRID:AB_2107448

This monoclonal targets GAPDH antibody [6C5]

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NNMT antibody (antibody)

RRID:AB_881715

This polyclonal targets NNMT

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Cyclin E antibody [HE12] (antibody)

RRID:AB_304167

This monoclonal targets Cyclin E

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