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Chromatin modification contributes to pluripotency maintenance in embryonic stem cells (ESCs). However, the related mechanisms remain obscure. Here, we show that Npac, a “reader” of histone H3 lysine 36 trimethylation (H3K36me3), is required to maintain mouse ESC (mESC) pluripotency since knockdown of Npac causes mESC differentiation. Depletion of Npac in mouse embryonic fibroblasts (MEFs) inhibits reprogramming efficiency. Furthermore, our chromatin immunoprecipitation followed by sequencing (ChIP-seq) results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs. Interestingly, we find that Npac interacts with positive transcription elongation factor b (p-TEFb), Ser2-phosphorylated RNA Pol II (RNA Pol II Ser2P), and Ser5-phosphorylated RNA Pol II (RNA Pol II Ser5P). Furthermore, depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rif1. Taken together, we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interacting with RNA Pol II Ser2P and Ser5P.

Jmjd6 is a conserved nuclear protein which possesses histone arginine demethylation and lysyl hydroxylase activity. Previous studies have revealed that Jmjd6 is essential for cell differentiation and embryo development. However, the role of Jmjd6 in mammalian ES cell identity and reprogramming has been unclear. Here we report that depletion of Jmjd6 not only results in downregulation of pluripotency genes but also is implicated in apoptosis, glycolysis, cell cycle and protein hydroxylation. We also revealed the reduction of BrdU incorporation in Jmjd6 depleted cells. Reprogramming efficiency of MEFs can be enhanced with Jmjd6 overexpression while the efficiency was reduced upon Jmjd6 depletion. Together, these results suggest that Jmjd6 can regulate ES cell homeostasis and enhance somatic cell reprogramming.

Post-translational modifications of histone proteins regulate a long cascade of downstream cellular activities, including transcription and replication. Cellular lineage differentiation involves large-scale intracellular signaling and extracellular context. In particular, histone modifications play instructive and programmatic roles in central nervous system development. Deciphering functions of histone could offer feasible molecular strategies for neural diseases caused by histone modifications. Here, we review recent advances of in vitro and in vivo studies on histone modifications in neural differentiation.

Liver cancer is the third most common cause of cancer death in the world. POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1/MAZR) is a transcription factor associated with various cancers. However, the role of PATZ1 in cancer progression remains controversial largely due to lack of genome-wide studies. Here we report that PATZ1 regulates cell proliferation by directly regulating CDKN1B (p27) in hepatocellular carcinoma cells. Our PATZ1 ChIP-seq and gene expression microarray analyses revealed that PATZ1 is strongly related to cancer signatures and cellular proliferation. We further discovered that PATZ1 depletion led to an increased rate of colony formation, elevated Ki-67 expression and greater S phase entry. Importantly, the increased cancer cell proliferation was accompanied with suppressed expression of the cyclin-dependent kinase inhibitor CDKN1B. Consistently, we found that PATZ1 binds to the genomic loci flanking the transcriptional start site of CDKN1B and positively regulates its transcription. Notably, we demonstrated that PATZ1 is a p53 partner and p53 is essential for CDKN1B regulation. In conclusion, our study provides novel mechanistic insights into the inhibitory role of PATZ1 in liver cancer progression, thereby yielding a promising therapeutic intervention to alleviate tumor burden.