The pluripotency-associated transcriptional network is regulated by a core circuitry of transcription factors. The PR domain-containing protein, PRDM14, maintains pluripotency by activating and ...repressing transcription in a target gene-dependent manner. However, the mechanisms underlying dichotomic switching of PRDM14-mediated transcriptional control remain elusive. Here, we identified C-terminal binding protein 1/2 (CtBP1/2) as a component of the PRDM14-mediated repressive complex. CtBP1/2 binding to PRDM14 depends on CBFA2T2, a core component of the PRDM14 complex. The loss of Ctbp1/2 impaired the PRDM14-mediated transcriptional repression required for pluripotency maintenance and transition from primed to naïve pluripotency. Furthermore, CtBP1/2 interacted with the PRC2 complexes, and the loss of Ctbp1/2 impaired PRC2 and H3K27me3 enrichment at target genes after Prdm14 induction. These results provide evidence that the target gene-dependent transcriptional activity of PRDM14 is regulated by partner switching to ensure the transition from primed to naïve pluripotency.
A noval anilino-pyrimidine fungicide, pyrimethanil butanedioic salt (C
28
H
32
N
6
O
4
), was synthesized by a chemical reaction of pyrimethanil and butanedioic acid. The low-temperature heat ...capacities of the compound were measured with an adiabatic calorimeter from 80 to 380 K. The thermodynamic function data relative to 298.15 K were calculated based on the heat capacity fitted curve. The thermal stability of the compound was investigated by TG and DSC. The TG curve shows that pyrimethanil butanedioic salt starts to sublimate at 455.1 K and totally changes into vapor when the temperature reaches 542.5 K with the maximal speed of weight loss at 536.8 K. The melting point, the molar enthalpy (Δ
fus
H
m
), and entropy (Δ
fus
S
m
) of fusion were determined from its DSC curves. The constant-volume energy of combustion (Δ
c
U
m
) of pyrimethanil butanedioic salt was measured by an isoperibol oxygen-bomb combustion calorimeter at
T
= (298.15 ± 0.001) K. From the Hess thermochemical cycle, the standard molar enthalpy of formation was derived and determined to be Δ
f
H
m
o
(pyrimethanil butanedioic salt)=−285.4 ± 5.5 kJ mol
−1
.
Epigenetic modifications, including DNA methylation and histone modifications, confer variety and stability of gene expression, which ensure the generation and maintenance of numerous distinctive ...cell types during mammalian development and in adults. Recent studies have suggested that genome-wide changes of epigenetic modifications, referred to as “epigenetic reprogramming,” occur during the development of primordial germ cells (PGCs) in mice. This reprogramming might be critical for the reestablishment of potential totipotency in this lineage. However, the molecular mechanisms underlying these events are just beginning to emerge. We briefly summarize here our current knowledge on the development of PGCs and their epigenetic reprogramming, which may have general implications for the reprogramming of somatic cell nuclei of any kind.
Although X chromosome transfer experiments indicated that tumor suppressor genes are present on the X chromosome, they have not been previously identified. In this report, we show that the ETS ...transcription factor MEF (ELF4), which is located on chromosome Xq26.1, possesses tumor suppressive capability. MEF expression was up-regulated by 5-azacytidine in some cancer cell lines. MEF overexpression induced morphological changes, such as the conversion of normally loose cell-cell contacts to strong interactions similar to those seen in the presence of matrix metalloproteinase (MMP) inhibitor BB94. In the colony formation assay, A549 cells, but not MEF-overexpressing cells, formed colonies in soft agar culture. Furthermore, MEF-overexpressing cells s.c. injected in the nude mice did not grow, whereas the control cells did. The A549 tumors were poorly differentiated, whereas the MEF-overexpressing tumors were well differentiated. By immunostaining with CD31, a marker on vascular endothelial cells, we found that tumor angiogenesis was significantly suppressed in the tumors formed from MEF-overexpressing cells. In addition, the conditioned media from A549 cell cultures stimulated the migration of human umbilical vein endothelial cells, whereas conditioned media from MEF-overexpressing cell cultures had less of an effect. By gelatin zymography, Western blotting analysis, and immunohistochemistry, we found that the expression levels of MMP-9 and MMP-2 were significantly reduced in MEF-overexpressing tumors. Immunohistochemical analyses showed that interleukin (IL)-8 expression was reduced in the MEF-overexpressing tumors in nude mice. Furthermore, IL-8 mRNA expression in vitro was significantly down-regulated in MEF-overexpressing cells, compared with A549 cells. MEF suppressed the transcription and promoter activities of the genes encoding MMP-9 and IL-8, whereas ETS-2 up-regulated these activities. Therefore, we propose that MEF is a candidate tumor suppressor gene on the X chromosome with activities that are opposite to those of ETS-2.
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