Although the negative regulator of nuclear import (NRNI) BRCA1 binding protein 2 (BRAP2) is highly expressed in testis, its role is largely unknown. Here we address this question by documenting the BRAP2 interactome from human testis, using the yeast 2-hybrid system to identify BRAP2-interacting proteins with roles in diverse cellular processes, including regulation of the actin cytoskeleton, u...

DNA methyltransferases (including DNMT1, DNMT3A and DNMT3B), catalyze the transfer of methyl groups from S-adenosyl-l-methionine to cytosine position 5; this methylation in promoter regions silences gene expression. In addition, DNMT1 plays a critical role in the maintenance of genomic DNA methylation during DNA replication. In the present study, silencing of DNMT1 with siRNA was performed in R...

Human DNA methyltransferase 1 (DNMT1) maintains the epigenetic state of DNA by replicating CpG methylation signatures from parent to daughter strands, producing heritable methylation patterns through cell divisions. The proposed catalytic mechanism of DNMT1 involves nucleophilic attack of Cys(1226) to cytosine (Cyt) C6, methyl transfer from S-adenosyl-l-methionine (SAM) to Cyt C5, and proton ab...

Bone loss induced by mechanical unloading is a common skeletal disease, but the precise mechanism remains unclear. The current study investigated role of histone methylation, key epigenetic marker, and its cross-talk with DNA methylation in bone unloading. expression G9a, ubiquitin-like PHD ring finger domains 1 (UHRF1), transferase (DNMT1) were increased hind limb (HLU) rats. This was accompan...

BACKGROUND We use our earlier experimental studies of the catalytic mechanism of DNA methyltransferases to prepare in silico a family of novel mechanism-based inhibitors of human Dnmt1. Highly specific inhibitors of DNA methylation can be used for analysis of human epigenome and for the creation of iPS cells. RESULTS We describe a set of adenosyl-1-methyl-pyrimidin-2-one derivatives as novel ...

Expression of the p16(Ink4a) tumor suppressor gene, a sensor of oncogenic stress, is up-regulated by a variety of potentially oncogenic stimuli in cultured primary cells. However, because p16(Ink4a) expression is also induced by tissue culture stress, physiological mechanisms regulating p16(Ink4a) expression remain unclear. To eliminate any potential problems arising from tissue culture-imposed...

Background: Defective ERK1 activity may regulate the DNA hypomethylation in T cells of lupus mice. Aims: To investigate function regulating and explore potential molecular mechanisms involved Methods: CD4+T were isolated from MRL/lpr BALB/c mice, activated in vitro presence or absence 5-azacytidine (5-Aza) (a methyltransferase inhibitor)/U0126 selective inhibitor ERK signaling...

DNA methyltransferase-1 (Dnmt1) is involved in the maintenance of DNA methylation patterns and is crucial for normal mammalian development. The aim of the present study was to assess the localization of Dnmt1 in cow, during the latest phases of oocyte differentiation and during the early stages of segmentation. Dnmt1 expression and localization were assessed in oocytes according to the chromati...

ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation...

Vertebrate DNA contains in addition to the four bases comprising the genetic information a modified base, 5-methyl cytosine that plays an important role in the epigenome. The methylated bases form a pattern of methylation that is cell specific and is faithfully inherited during cell division. The enzyme DNA methyltransferase 1 DNMT1 is responsible for copying the DNA methylation pattern but oth...