OBJECTIVE Class IIa histone deacetylases (HDACs) belong to a large family of enzymes involved in protein deacetylation and play a role in regulating gene expression and cell differentiation. Previously, we showed that HDAC inhibitors modify the timing and determination of pancreatic cell fate. The aim of this study was to determine the role of class IIa HDACs in pancreas development. RESEARCH...

In patients with heart failure, reactivation of a fetal gene program, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a hallmark for maladaptive remodeling of the LV. The mechanisms that regulate this reactivation are incompletely understood. Histone acetylation and methylation affect the conformation of chromatin, which in turn governs the accessibility of DN...

Background: Mutation of p53 is a frequent event, and mutant exhibits low levels acetylation phosphorylation. This study aimed to investigate the effect histone deacetylase (HDAC) inhibitor, 4-hexylresorcinol (4HR), on phosphorylation carcinoma cells its therapeutic effects in xenograft model. Methods: To determine 4HR p53, western blot analysis was performed using YD-9 YD-15 cells. siRNA used e...

VSMCs (vascular smooth muscle cells) dedifferentiate from the contractile to the synthetic phenotype in response to acute vascular diseases such as restenosis and chronic vascular diseases such as atherosclerosis, and contribute to growth of the neointima. We demonstrated previously that balloon catheter injury of rat carotid arteries resulted in increased expression of CaMKII (Ca(2+)/calmoduli...

The delta(B) and delta(C) splice variants of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), which differ by the presence of a nuclear localization sequence, are both expressed in cardiomyocytes. We used transgenic (TG) mice and CaMKII expression in cardiomyocytes to test the hypothesis that the CaMKIIdelta(C) isoform regulates cytosolic Ca(2+) handling and the delta(B) isoform, which l...

Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mappin...

Glutamine-rich sequences exist in a wide range of proteins across multiple species. A subset of glutamine-rich sequences has been shown to form amyloid fibers implicated in human diseases. The physiological functions of these sequence motifs are not well understood, partly because of the lack of structural information. Here we have determined a high-resolution structure of a glutamine-rich doma...

For the past decade protein acetylation has been shown to be a crucial post-transcriptional modification involved in the regulation of protein functions. Histone acetyltransferases (HATs) mediate acetylation of histones which results in the nucleosomal relaxation associated with gene expression. The reverse reaction, histone deacetylation, is mediated by histone deacetylases (HDACs) leading to ...

In embryonic cardiomyocytes, sarcoplasmic reticulum (SR)-derived Ca2+ release is required to induce Ca2+ oscillations for contraction and to control cardiac development through Ca2+ -activated pathways. Here, our aim was to study how SR Ca2+ release regulates cytosolic and nuclear Ca2+ distribution and the subsequent effects on the Ca2+ -dependent localization of class IIa histone deacetylases ...

The nuclear receptor vitamin D receptor (VDR) is known to associate with two vitamin D response element (VDRE) containing chromatin regions of the insulin-like growth factor binding protein 3 (IGFBP3) gene. In non-malignant MCF-10A human mammary cells, we show that the natural VDR ligand 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)) causes cyclical IGFBP3 mRNA accumulation with a periodicity o...