The transcriptional cofactor MCAF1/ATF7IP is involved in histone gene expression and cellular senescence.

Cellular senescence is post-mitotic or oncogene-induced events combined with nuclear remodeling. MCAF1 (also known as hAM or ATF7IP), a transcriptional cofactor that is overexpressed in various cancers, functions in gene activation or repression, depending on interacting partners. In this study, we found that MCAF1 localizes to PML nuclear bodies in human fibroblasts and non-cancerous cells.

The role of methyl-binding proteins in chromatin organization and epigenome maintenance.

Methylated DNA can be specifically recognized by a set of proteins called methyl-CpG-binding proteins (MBPs), which belong to three different structural families in mammals: the MBD family, the Kaiso and Kaiso-like proteins and the SRA domain proteins. A current view is that, once bound to methylated DNA, MBPs translate the DNA methylation signal into appropriate functional states, through interactions with diverse partners. However, if some of the biological functions of MBPs have been widely described--notably transcriptional repression--others are poorly understood, and more generally the extent of MBP activities remains unclear.

The human proteins MBD5 and MBD6 associate with heterochromatin but they do not bind methylated DNA.

Background: MBD5 and MBD6 are two uncharacterized mammalian proteins that contain a putative Methyl-Binding Domain (MBD). In the proteins MBD1, MBD2, MBD4, and MeCP2, this domain allows the specific recognition of DNA containing methylated cytosine; as a consequence, the proteins serve as interpreters of DNA methylation, an essential epigenetic mark. It is unknown whether MBD5 or MBD6 also bind methylated DNA; this question has interest for basic research, but also practical consequences for human health, as MBD5 deletions are the likely cause of certain cases of mental retardation.

Sequence-specific recognition of methylated DNA by human zinc-finger proteins.

DNA methylation is an essential epigenetic mark. Three classes of mammalian proteins recognize methylated DNA: MBD proteins, SRA proteins and the zinc-finger proteins Kaiso, ZBTB4 and ZBTB38. The last three proteins can bind either methylated DNA or unmethylated consensus sequences; how this is achieved is largely unclear.

Many paths to one goal? The proteins that recognize methylated DNA in eukaryotes.

DNA methylation is an epigenetically inherited chemical modification that is associated with transcriptional silencing and is essential for mammalian development. The DNA methylation signal is read out by methyl-CpG binding proteins (MBPs) that specifically bind to methylated DNA. Three structurally divergent families of MBPs have been identified so far: the MBD family, the SRA family and a family of proteins with Zinc fingers.

The Drosophila jumonji gene encodes a JmjC-containing nuclear protein that is required for metamorphosis.

Jumonji (Jmj) is a transcriptional repressor that plays important roles in the suppression of cell proliferation and development of various tissues in the mouse. To further clarify the roles of Jmj during development and gain insight into mechanisms of Jmj-mediated transcriptional regulation, we have taken advantage of Drosophila as a model organism. Drosophila Jmj (dJmj) shares high homology with mammalian Jmj in the JmjN, JmjC and AT-rich interaction domains, as well as in the N-terminal repression domain.

Identification of ZNF200 as a novel binding partner of histone H3 methyltransferase G9a.

G9a belongs to the subfamily of histone H3 lysine 9 (H3-K9)-specific methyltransferases. On amino acid sequence alignment of human and Drosophila G9a, we found that the N-terminal region from amino acids 532-605 to be evolutionarily conserved and named this the G9a homology domain (GHD). Using the GHD of human G9a (hG9a) as a bait, we isolated cDNA encoding a zinc finger protein 200 (ZNF200), which contains five C(2)H(2)-type zinc finger domains in tandem arrays.

Identification of a novel BTB-zinc finger transcriptional repressor, CIBZ, that interacts with CtBP corepressor.

The transcriptional corepressor C-terminal binding protein (CtBP) is thought to be involved in development and oncogenesis, but the regulation of its corepressor activity is largely unknown. We show here that a novel BTB-zinc finger protein, CIBZ (CtBP-interacting BTB zinc finger protein; a mouse ortholog of rat ZENON that was recently identified as an e-box/dyad binding protein), redistributes CtBP to pericentromeric foci from a diffuse nuclear localization in interphase cells. CIBZ physically associates with CtBP via a conserved CtBP binding motif, PLDLR.