Systematic identification of factors involved in the silencing of germline genes in mouse embryonic stem cells.

In mammals, many germline genes are epigenetically repressed to prevent their illegitimate expression in somatic cells. To advance our understanding of the mechanisms restricting the expression of germline genes, we analyzed their chromatin signature and performed a CRISPR-Cas9 knock-out screen for genes involved in germline gene repression using a Dazl-GFP reporter system in mouse embryonic stem cells (mESCs). We show that the repression of germline genes mainly depends on the polycomb complex PRC1.

Development and Validation of Antibodies Targeting Site-Specific Histone Methylation.

The development of specific anti-modification antibodies as research tools has revolutionized the way histone methylation is studied. Lack of stringent quality controls, however, led to the development of nonspecific antibodies, compromising their use. In this chapter, we provide a series of protocols that collectively will help those studying histone methylation to develop and thoroughly validate high-end sequence-specific and methylation-dependent antibodies.

Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation.

Chromodomain helicase DNA binding protein 4 (CHD4) is an ATPase subunit of the Nucleosome Remodelling and Deacetylation (NuRD) complex that regulates gene expression. CHD4 is essential for growth of multiple patient derived melanoma xenografts and for breast cancer. Here we show that CHD4 regulates expression of PADI1 (Protein Arginine Deiminase 1) and PADI3 in multiple cancer cell types modulating citrullination of arginine residues of the allosterically-regulated glycolytic enzyme pyruvate kinase M2 (PKM2).

Succinylation of H3K122 destabilizes nucleosomes and enhances transcription.

Histone post-translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role in transcription. In this study, we characterize the role of an acylation on the lateral surface of the histone octamer, H3K122 succinylation (H3K122succ), in chromatin function and transcription.

Author Correction: H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.

In this article, the Ponceau staining presented in Fig. 1b (right, bottom) does not follow best practices for figure preparation since itinadvertently included duplications from the Ponceau staining presented in Supplementary Fig. 1b (for which the same preparation ofnucleosomes from HeLa cells had been used).