Klf4 methylated by Prmt1 restrains the commitment of primitive endoderm.

The second cell fate decision in the early stage of mammalian embryonic development is pivotal; however, the underlying molecular mechanism is largely unexplored. Here, we report that Prmt1 acts as an important regulator in primitive endoderm (PrE) formation. First, Prmt1 depletion promotes PrE gene expression in mouse embryonic stem cells (ESCs).

Hyperthermia depletes Oct4 in mouse blastocysts and stem cells.

Temperature is an important microenvironmental factor that functions epigenetically in normal embryonic development. However, the effect of hyperthermia in the stem cells is not fully understood. Oct4 is a tightly regulated master regulator of pluripotency maintenance in stem cells and during early embryonic development.

PRMT1 activates myogenin transcription via MyoD arginine methylation at R121.

MyoD is a determining transcription factor involved in myogenic cell differentiation. Post translational modifications of MyoD, including phosphorylation and acetylation, can regulate its transcription activity. Inhibition of protein arginine methyltransferase 1 (PRMT1) leads to insufficient muscle differentiation.

Methylation of C/EBPα by PRMT1 Inhibits Its Tumor-Suppressive Function in Breast Cancer.

C/EBPα is an essential transcription factor involved in regulating the expression or function of certain cell-cycle regulators, including in breast cancer cells. Although protein arginine methyltransferases have been shown to play oncogenic roles in a variety of cancers, little is known about the role of arginine methylation in regulating the antiproliferation activity of C/EBPα. Here, we report that the protein arginine methyltransferase 1 (PRMT1) is overexpressed in human breast cancer and that elevated PRMT1 correlates with cancer malignancy.

PCAF-mediated acetylation of Lin28B increases let-7 biogenesis in lung adenocarcinoma H1299 cells.

Background: Lin28B and its paralog Lin28A are small RNA binding proteins that have similar inhibitory effects, although they target separate steps in the maturation of let-7 miRNAs in mammalian cells. Because Lin28B participates in the promotion and development of tumors mostly by blocking the let-7 tumor suppressor family members, we sought to explore the associated mechanisms to gain insights into how Lin28B might be decreased in human cancer cells to increase let-7 levels and reverse malignancy.

Results: We demonstrated that the histone acetyltransferase PCAF, via its cold shock domain, directly interacts with and subsequently acetylates Lin28B in lung adenocarcinoma-derived H1299 cells.

CRIF1 enhances p53 activity via the chromatin remodeler SNF5 in the HCT116 colon cancer cell lines.

CR6-interacting factor 1 (CRIF1) is ubiquitously expressed in human tissues. CRIF1 was first identified as a Gadd45γ (also known as CR6)-interacting protein, and it was also identified in a human colon cancer cell line stably transformed with p53. These results suggested that CRIF1 functions in the nucleus with p53 and Gadd45 family proteins in the suppression of cell growth and tumor development.

C/EBPα negatively regulates SIRT7 expression via recruiting HDAC3 to the upstream-promoter of hepatocellular carcinoma cells.

Mammalian Sirtuin proteins (SIRTs) are homologs of yeast Sir2, and characterized as class III histone deacetylases of NAD(+) dependence. Unlike their lower counterparts that are directly involved in the extending of lifespan, mammalian SIRTs mainly function in metabolism and cellular homeostasis, among them, SIRT7 is the least understood. SIRT7 is localized in the nucleus and rich in nucleoli associated with RNA polymerase I, and correlated with cell proliferation.

Specific phosphorylation of histone demethylase KDM3A determines target gene expression in response to heat shock.

Histone lysine (K) residues, which are modified by methyl- and acetyl-transferases, diversely regulate RNA synthesis. Unlike the ubiquitously activating effect of histone K acetylation, the effects of histone K methylation vary with the number of methyl groups added and with the position of these groups in the histone tails. Histone K demethylases (KDMs) counteract the activity of methyl-transferases and remove methyl group(s) from specific K residues in histones.

Human PIH1 associates with histone H4 to mediate the glucose-dependent enhancement of pre-rRNA synthesis.

Ribosome biogenesis is critical in the growth of eukaryotic cells, in which the synthesis of precursor ribosomal RNA is the first and rate-limiting step. Here, we show that human PIH1 domain-containing protein 1 (PIH1) interacts directly with histone H4 and recruits the Brg1-SWI/SNF complex via SNF5 to human rRNA genes. This process is likely involved in PIH1-dependent DNase I-hypersensitive chromatin remodeling at the core promoter of the rRNA genes.

A switch from hBrm to Brg1 at IFNγ-activated sequences mediates the activation of human genes.

The SWI/SNF chromatin-remodeling complexes utilize energy from ATP hydrolysis to reposition nucleosomes and regulate the expression of human genes. Here, we studied the roles of human Brahma (hBrm) and Brahma-related gene 1 (Brg1), the ATPase subunits of the SWI/SNF complexes, in regulating human genes. Our results indicate that both hBrm and Brg1 interact with Signal transducer and activator of transcription (Stat) 1 in vitro.

Stat1 mediates an auto-regulation of hsp90beta gene in heat shock response.

We have reported earlier that a heat shock element in the first intron of human hsp90beta gene (iHSE) acts as an intronic enhancer to bind the heat shock factor (HSF1) and activates hsp90beta gene under heat shock. Here, we show that, in addition to the HSF1, Stat1 phosphorylation is indispensable in the event. We show that Jak2, a Janus kinase specifically associated with the beta subunit of IFNgamma receptor, and PKCepsilon an isoform of the atypical PKC family, are the two dominant kinases responsible for the heat shock induced phosphorylation on Y701 and S727 of Stat1.

[Heat shock induced the expression of major histocompatibility complex class transactivator and human leukocyte antigen-DR in Jurkat cells].

Objective: To explore the effect of a non-lethal heat shock, in comparison with the treatment of interferon-gamma (IFN gamma), on the expression of major histocompatibility complex transactivator (CTA) and its downstream target gene of the human leukocyte antigens (HLA)-DR in Jurkat cells.

Methods: The changes of CTA mRNA in Jurkat cells before and after the treatment of heat shock or IFN gamma were detected using real time RT-PCR. The changes of CTA protein were detected with Western blot.

Sequential recruitment of PCAF and BRG1 contributes to myogenin activation in 12-O-tetradecanoylphorbol-13-acetate-induced early differentiation of rhabdomyosarcoma-derived cells.

Myogenin and its upstream regulator MyoD are known to be required for myogenic cell differentiation. Although both of them can be expressed in rhabdomyosarcoma-derived RD cells, the cells are unable to undergo full-scale terminal myogenic differentiation. 12-O-Tetradecanoylphorbol-13-acetate (TPA) has been found to be functional in the induction of RD cell differentiation, whereas its mechanism is not fully understood.