The C-terminal 4CXXC-type zinc finger domain of CDCA7 recognizes hemimethylated DNA and modulates activities of chromatin remodeling enzyme HELLS.

The chromatin-remodeling enzyme helicase lymphoid-specific (HELLS) interacts with cell division cycle-associated 7 (CDCA7) on nucleosomes and is involved in the regulation of DNA methylation in higher organisms. Mutations in these genes cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, which also results in DNA hypomethylation of satellite repeat regions. We investigated the functional domains of human CDCA7 in HELLS using several mutant CDCA7 proteins.

Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells.

DNA methylation, repressive histone modifications, and PIWI-interacting RNAs are essential for controlling retroelement silencing in mammalian germ lines. Dysregulation of retroelement silencing is associated with male sterility. Although retroelement silencing mechanisms have been extensively studied in mouse germ cells, little progress has been made in humans.

Erratum: Derepression of inflammation-related genes link to microglia activation and neural maturation defect in a mouse model of Kleefstra syndrome.

[This corrects the article DOI: 10.1016/j.isci.

Derepression of inflammation-related genes link to microglia activation and neural maturation defect in a mouse model of Kleefstra syndrome.

Haploinsufficiency of , which encodes histone H3 lysine 9 (H3K9) methyltransferase G9a-like protein (GLP), causes Kleefstra syndrome (KS), a complex disorder of developmental delay and intellectual disability. Here, we examined whether postnatal supply of GLP can reverse the neurological phenotypes seen in mice as a KS model. Ubiquitous GLP supply from the juvenile stage ameliorated behavioral abnormalities in mice.

Regulation of mammalian 3D genome organization and histone H3K9 dimethylation by H3K9 methyltransferases.

Histone H3 lysine 9 dimethylation (H3K9me2) is a highly conserved silencing epigenetic mark. Chromatin marked with H3K9me2 forms large domains in mammalian cells and overlaps well with lamina-associated domains and the B compartment defined by Hi-C. However, the role of H3K9me2 in 3-dimensional (3D) genome organization remains unclear.

The fibronectin type-III (FNIII) domain of ATF7IP contributes to efficient transcriptional silencing mediated by the SETDB1 complex.

Background: The histone methyltransferase SETDB1 (also known as ESET) represses genes and various types of transposable elements, such as endogenous retroviruses (ERVs) and integrated exogenous retroviruses, through a deposition of trimethylation on lysine 9 of histone H3 (H3K9me3) in mouse embryonic stem cells (mESCs). ATF7IP (also known as MCAF1 or AM), a binding partner of SETDB1, regulates the nuclear localization and enzymatic activities of SETDB1 and plays a crucial role in SETDB1-mediated transcriptional silencing. In this study, we further dissected the ATF7IP function with its truncated mutants in Atf7ip knockout (KO) mESCs.

ATF7IP regulates SETDB1 nuclear localization and increases its ubiquitination.

Understanding of the appropriate regulation of enzymatic activities of histone-modifying enzymes remains poor. The lysine methyltransferase, SETDB1, is one of the enzymes responsible for the methylation of histone H3 at lysine 9 (H3K9) and plays a key role in H3K9 trimethylation-mediated silencing of genes and retrotransposons. Here, we reported that how SETDB1's enzymatic activities can be regulated by the nuclear protein, ATF7IP, a known binding partner of SETDB1.

G9a-dependent histone methylation can be induced in G1 phase of cell cycle.

Epigenetic information (epigenome) on chromatin is crucial for the determination of cellular identity and for the expression of cell type-specific biological functions. The cell type-specific epigenome is maintained beyond replication and cell division. Nucleosomes of chromatin just after DNA replication are a mixture of old histones with the parental epigenome and newly synthesized histones without such information.

Biochemical validation of EHMT1 missense mutations in Kleefstra syndrome.

Kleefstra syndrome (KS) (9q34 deletion syndrome) is a rare autosomal dominant disorder characterized by intellectual disability, frequently coupled with a spectrum of complex physical and clinical manifestations. As the euchromatic histone methyltransferase-1 gene (EHMT1, GLP, or KMT1D) within the 9q34 region is deleted or mutated in most of the individuals with KS, its absence or defect in one allele is speculated to cause the major symptoms of the syndrome. Most of the EHMT1 mutations are frameshift or nonsense mutations, but two individuals with KS were reported to possess EHMT1 missense mutations.