@article {119, title = {Cardiac-specific β-catenin deletion dysregulates energetic metabolism and mitochondrial function in perinatal cardiomyocytes.}, journal = {Mitochondrion}, volume = {60}, year = {2021}, month = {2021 09}, pages = {59-69}, abstract = {

β-Catenin signaling pathway regulates cardiomyocytes proliferation and differentiation, though its involvement in metabolic regulation of cardiomyocytes remains unknown. We used one-day-old mice with cardiac-specific knockout of β-catenin and neonatal rat ventricular myocytes treated with β-catenin inhibitor to investigate the role of β-catenin metabolism regulation in perinatal cardiomyocytes. Transcriptomics of perinatal β-catenin-ablated hearts revealed a dramatic shift in the expression of genes involved in metabolic processes. Further analysis indicated an inhibition of lipolysis and glycolysis in both in vitro and in vivo models. Finally, we showed that β-catenin deficiency leads to mitochondria dysfunction via the downregulation of Sirt1/PGC-1α pathway. We conclude that cardiac-specific β-catenin ablation disrupts the energy substrate shift that is essential for postnatal heart maturation, leading to perinatal lethality of homozygous β-catenin knockout mice.

}, issn = {1872-8278}, doi = {10.1016/j.mito.2021.07.005}, author = {Balatskyi, Volodymyr V and Vaskivskyi, Vasyl O and Myronova, Anna and Avramets, Diana and Nahia, Karim Abu and Macewicz, Larysa L and Ruban, Tetiana P and Kucherenko, Dar{\textquoteright}ya Yu and Soldatkin, Oleksandr O and Lushnikova, Iryna V and Skibo, Galyna G and Winata, Cecilia L and Dobrzyn, Pawel and Piven, Oksana O} } @article {Lanny Winata:2015-04-01T00:00:00:1389-2029:117, title = {Changing Faces of Transcriptional Regulation Reflected by Zic3}, journal = {Current Genomics}, volume = {16}, year = {2015}, month = {02/2015}, pages = {117-127}, abstract = {

The advent of genomics in the study of developmental mechanisms has brought a trove of information on gene datasets and regulation during development, where the Zic family of zinc-finger proteins plays an important role. Genomic analysis of the modes of action of Zic3 in pluripotent cells demonstrated its requirement for maintenance of stem cells pluripotency upon binding to the proximal regulatory regions (promoters) of genes associated with cell pluripotency (Nanog, Sox2, Oct4, etc.) as well as cell cycle, proliferation, oncogenesis and early embryogenesis. In contrast, during gastrulation and neurulation Zic3 acts by binding the distal regulatory regions (enhancers, etc) associated with control of gene transcription in the Nodal and Wnt signaling pathways, including genes that act to break body symmetry. This illustrates a general role of Zic3 as a transcriptional regulator that acts not only alone, but in many instances in conjunction with other transcription factors. The latter is done by binding to adjacent sites in the context of multi-transcription factor complexes associated with regulatory elements.

}, keywords = {ZDGaffiliated}, url = {http://www.ingentaconnect.com/content/ben/cg/2015/00000016/00000002/art00011}, author = {Winata, Cecilia L and Kondrychyn, Igor and Korzh, Vladimir} } @article {69, title = {Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos.}, journal = {Int J Dev Biol}, volume = {54}, year = {2010}, month = {2010}, pages = {803-13}, abstract = {

Embryo development proceeds from a cascade of gene activation and repression events controlled by epigenetic modifications of DNA and histones. Little is known about epigenetic states in the developing zebrafish, despite its importance as a model organism. We report here DNA methylation and histone modification profiles of promoters of developmentally-regulated genes (pou5f1, sox2, sox3, klf4, nnr, otx1b, nes, vasa), as well as tert and bactin2, in zebrafish embryos at the mid-late blastula transition, shortly after embryonic genome activation. We identify four classes of promoters based on the following profiles: (i) those enriched in marks of active genes (H3K9ac, H4ac, H3K4me3) without transcriptionally repressing H3K9me3 or H3K27me3; (ii) those enriched in H3K9ac, H4ac and H3K27me3, without H3K9me3; one such gene was klf4, shown by in situ hybridization to be mosaically expressed, likely accounting for the detection of both activating and repressive marks on its promoter; (iii) those enriched in H3K4me3 and H3K27me3 without acetylation; and (iv) those enriched in all histone modifications examined. Culture of embryo-derived cells under differentiation conditions leads to H3K9 and H4 deacetylation and H3K9 and H3K27 trimethylation on genes that are inactivated, yielding an epigenetic profile similar to those of fibroblasts or muscle. All promoters however retain H3K4me3, indicating an uncoupling of H3K4me3 occupancy and gene expression. All non-CpG island developmentally-regulated promoters are DNA unmethylated in embryos, but hypermethylated in fibroblasts. Our results suggest that differentially expressed embryonic genes are regulated by various patterns of histone modifications on unmethylated DNA, which create a developmentally permissive chromatin state.

}, keywords = {Animals, Blastula, Cell Line, Chromatin, Chromatin Immunoprecipitation, CpG Islands, DNA Methylation, Embryo, Nonmammalian, Fibroblasts, Gene Expression Profiling, Gene Expression Regulation, Developmental, Histones, In Situ Hybridization, Lysine, Methylation, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Zebrafish, Zebrafish Proteins}, issn = {1696-3547}, doi = {10.1387/ijdb.103081ll}, author = {Lindeman, Leif C and Winata, Cecilia L and Aanes, Hvard and Mathavan, Sinnakaruppan and Alestrom, Peter and Collas, Philippe} }