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The manipulation of chromatin structure regulates gene expression and the flow of genetic information. Histone modifications and ATP-dependent chromatin remodeling together with DNA methylation are dynamic processes that modify chromatin architecture and profoundly modulate gene expression. Their coordinated control is key to ensuring proper cell commitment(More)
p300 and CBP are general transcriptional coactivators implicated in different cellular processes, including regulation of the cell cycle, differentiation, tumorigenesis, and apoptosis. Posttranslational modifications such as phosphorylation are predicted to select a specific function of p300/CBP in these processes; however, the identification of the kinases(More)
Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in pathological cardiac hypertrophy, but the mechanisms by which it modulates gene activity in the nucleus to mediate hypertrophic signaling remain unclear. Here, we report that nuclear CaMKII activates cardiac transcription by directly binding to chromatin and regulating the(More)
Primary microcephaly (PM) is a developmental disorder of early neuroprogenitors that results in reduction of the brain mass, particularly the cortex. To gain fresh insight into the pathogenesis of PM, we describe a consanguineous family with a novel genetic variant responsible for the disease. We performed autozygosity mapping followed by exome sequencing(More)
The transcription of tissue-specific genes is controlled by regulatory factors and cofactors and is suppressed in cardiac cells by the antineoplastic agent doxorubicin. Here we show that exposure of cultured cardiomyocytes to doxorubicin resulted in the rapid depletion of transcripts for MEF2C, dHAND, and NKX2.5, three pivotal regulators of cardiac gene(More)
Embryonic lethality is a recognized phenotypic expression of individual gene mutations in model organisms. However, identifying embryonic lethal genes in humans is challenging, especially when the phenotype is manifested at the preimplantation stage. In an ongoing effort to exploit the highly consanguineous nature of the Saudi population to catalog(More)
Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood. Using mice with genetic ablation of calcium/calmodulin-dependent protein kinase II δ(More)
The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the heart and in cardiac diseases remains unknown. To investigate the in vivo role of LMPTP in cardiac function, we generated mice with genetic inactivation of the Acp1 locus and studied their response to(More)
Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy causing systolic dysfunction and heart failure. Rare variants in more than 30 genes, mostly encoding sarcomeric proteins and proteins of the cytoskeleton, have been implicated in familial DCM to date. Yet, the majority of variants causing DCM remain to be identified. The goal of the study is to(More)
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