| 2018 |
MTF2 directly binds DNA in a methylation-sensitive manner, selectively recognizing regions with high density of unmethylated CpGs in a context of reduced helix twist, and is essential for genome-wide recruitment of the PRC2 catalytic subunit EZH2 to target genes in mouse embryonic stem cells; MTF2 knockout abolishes EZH2 recruitment and greatly reduces H3K27me3 deposition. |
MTF2 knockout ESCs, ChIP-seq for EZH2 and H3K27me3, in vitro DNA binding assays, genome-wide analysis of CpG methylation and helix twist |
Nature genetics |
High |
29808031
|
| 2011 |
MTF2 is a component of the PRC2 complex in mouse ES cells and, together with JARID2 and esPRC2p48, synergistically stimulates the histone methyltransferase activity of PRC2 in vitro; knockdown of MTF2 alters H3K27 methylation levels and causes expression of differentiation-associated genes. |
Co-immunoprecipitation, in vitro histone methyltransferase assay with reconstituted PRC2 complex, siRNA knockdown in ES cells, gene expression analysis |
Stem cells (Dayton, Ohio) |
High |
21732481
|
| 2010 |
Pcl2/Mtf2 forms a complex with PRC2 and binds to Hox gene loci in a PRC2-dependent manner; it is required for PRC2-mediated Hox gene repression and exhibits a synergistic effect on PRC1-mediated Hox repression without major alterations in H3K27me3 or PRC1 deposition; paradoxically, in embryonic fibroblasts Pcl2 activates Cdkn2a expression by locally suppressing PRC2 catalytic activity. |
Co-immunoprecipitation, ChIP, conditional knockout and knockdown mouse genetics, gene expression analysis |
Molecular and cellular biology |
High |
21059868
|
| 2004 |
Chick Pcl2 (ortholog of MTF2) functions as a transcriptional repressor through its PHD finger domain; it directly interacts with EZH2 (a PRC2 component) via pulldown assay, represses Shh promoter activity in vitro, and regulates left-right axis patterning in chick embryos by silencing Shh expression in the right side of Hensen's node. |
In vitro pulldown assay (PHD finger–EZH2 interaction), in vitro transcription repression mapping, gain- and loss-of-function in chick embryos, luciferase reporter assay for Shh promoter |
Development (Cambridge, England) |
High |
15294861
|
| 2018 |
MTF2-PRC2 directly represses MDM2 in hematopoietic cells; loss of MTF2 results in overexpression of MDM2, which inhibits p53, leading to defects in cell-cycle regulation and apoptosis and chemoresistance in AML; overexpression of MTF2 or MDM2 inhibitors restored p53 activity and chemosensitivity. |
MTF2 overexpression/knockdown in CD34+CD38- AML cells, ChIP-seq, patient-derived xenograft mouse model, MDM2 inhibitor treatment, gene expression and apoptosis assays |
Cancer discovery |
Medium |
30115703
|
| 2018 |
Mtf2 is required for maintenance of core PRC2 protein levels and global H3K27me3 at promoter-proximal regions in erythroid progenitors; Mtf2-knockout embryos show global loss of H3K27me3, de-repression of canonical Wnt signaling, and die by e15.5 due to severe anemia; chemical inhibition of Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro. |
Conditional Mtf2 knockout mice, ChIP-seq for H3K27me3, Western blot for PRC2 core proteins, gene regulatory network analysis, chemical Wnt inhibitor rescue in vitro |
Cell discovery |
High |
29736258
|
| 2011 |
PCL2 depletion in ESCs leads to decreased H3K27me3 at promoters of pluripotency transcription factors Tbx3, Klf4, and Foxd3, with concomitant upregulation of these genes, which subsequently activate Oct4, Nanog, and Sox2 through a feed-forward circuit, increasing self-renewal and delaying differentiation. |
siRNA knockdown in mouse ESCs, ChIP for H3K27me3 at specific promoters, gene expression analysis, flow cytometry for pluripotency markers |
Cell cycle (Georgetown, Tex.) |
Medium |
21193838
|
| 2025 |
MTF2 stimulates PRC2 histone methyltransferase (HMT) activity in vitro using reconstituted substrates; MTF2 promotes PRC2 chromatin-binding activity in a DNA-sequence-dependent manner (GCN-rich sequences); MTF2 together with JARID2 and EPOP fosters PRC2-mediated H3K27me3 deposition at chromatin nucleation sites. |
In vitro HMT assay with reconstituted PRC2, binding assays with reconstituted dinucleosome substrates, EED-rescue system in vivo for chromatin recruitment |
Proceedings of the National Academy of Sciences of the United States of America |
High |
41650228
|
| 2018 |
PCL2 protects p53 from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus, thereby elevating p53 protein stability and increasing expression of p53 target genes in breast cancer cells. |
PCL2 overexpression and knockdown in breast cancer cells, co-immunoprecipitation, ubiquitination assay, Western blot, subcellular fractionation/immunofluorescence for MDM2 nucleolar localization |
Science bulletin |
Medium |
36658883
|
| 2024 |
MTF2 directly binds to EZH2 in osteosarcoma cells and promotes EZH2-mediated silencing of SFRP1, thereby activating Wnt signaling to drive osteosarcoma progression; EZH2 upregulation or SFRP1 antagonism counteracted effects of MTF2 knockdown. |
Co-immunoprecipitation (Co-IP) assay for MTF2-EZH2 interaction, siRNA knockdown, Western blot, cell proliferation/invasion/apoptosis assays, rescue experiments |
Journal of orthopaedic surgery and research |
Low |
39118123
|
| 2025 |
PCIF1-mediated m6Am methylation at the MTF2 mRNA 5' cap selectively suppresses MTF2 translation; PCIF1 knockdown reduces OSCC progression, while MTF2 knockdown counteracts this protective effect, placing MTF2 downstream of PCIF1 in a post-transcriptional regulatory axis. |
m6Am methylation mapping, PCIF1 knockdown and MTF2 knockdown in OSCC cell lines and in vivo mouse models, Western blot for MTF2 protein, polysome profiling (implied), rescue assays |
Clinical and translational medicine |
Medium |
40156159
|
| 2025 |
MTF2 stimulates PRC2.1-mediated repression in human pluripotent stem cells and cardiac differentiation through its interactions with both DNA and H3K36me3; MTF2-PRC2.1 maintains normal cardiomyocyte function and action potential rhythm; PHF19 antagonizes MTF2 function in this context. |
Separation-of-function mutants in human PSCs, ChIP-seq for H3K27me3, cardiomyocyte differentiation assays, electrophysiology for action potential measurement |
bioRxivpreprint |
Medium |
|
| 2025 |
De novo DNA methylation at bivalent promoters leads to reduced MTF2 binding and eviction of H3K27me3, resulting in gene activation; this demonstrates that MTF2 binding to unmethylated CpG-rich regions is required for maintaining H3K27me3 at bivalent loci. |
Hit-and-run CRISPR/dCas9 epigenome editing to deposit DNA methylation, ChIP-seq for MTF2 and H3K27me3, comparison of methylated vs. unmethylated promoters |
bioRxivpreprint |
Medium |
|
| 2024 |
EPOP disrupts the PRC2.1 dimer and reduces chromatin association; an EPOP mutant defective in PRC2 binding enhances genome-wide enrichment of MTF2 and H3K27me3, indicating that MTF2-PRC2.1 dimerization contributes to its avidity-dependent chromatin binding. |
EPOP PRC2-binding mutant in mouse epiblast-like cells, ChIP-seq for MTF2 and H3K27me3, biochemical analysis of PRC2.1 oligomerization state |
bioRxivpreprint |
Low |
|