Posts Tagged: transcription factors

Maintaining Ancient Organelles: Mitochondrial Biogenesis and Maturation

Maintaining Ancient Organelles: Mitochondrial Biogenesis and Maturation

Rick B. Vega, Julie L. Horton, Daniel P. Kelly

Peroxisome-proliferator activated receptor γ (PPARγ) coactivator-1α (PGC-1α) mediates physiological control of mitochondrial biogenesis and function. The transcriptional coactivator PGC-1α interacts directly with multiple transcription factors to integrate upstream signaling events with mitochondrial biogenesis and functional capacity. The downstream transcription factors control virtually every aspect of mitochondrial function and energy production, including biogenesis, dynamics, and maintenance of protein levels. The control of PGC-1α expression and activity is dynamic, responding to multiple intracellular second messengers and signaling molecules transmitting inputs from various physiological and metabolic stimuli (top). AMPK indicates AMP-activated protein kinase; CaMK, calmodulin-dependent kinase; CN, calcineurin; CREB, cAMP-response element binding protein; ERR, estrogen-related receptor; ETC/OXPHOS, electron transport chain/oxidative phosphorylation; NAD+, nicotinamide adenine dinucleotide; and NRF, nuclear respiratory factor. [Powerpoint FIle]

Maintaining Ancient Organelles: Mitochondrial Biogenesis and Maturation

Maintaining Ancient Organelles: Mitochondrial Biogenesis and Maturation

Rick B. Vega, Julie L. Horton, Daniel P. Kelly

Two predominant models of mtDNA replication are shown here. Both models concur the replisome consists of at least a helicase, T7 gp4-like protein with intramitochondrial nucleoid localization (TWINKLE; orange) and polymerase γ (POLG; yellow). Leading strand synthesis begins at OH and lagging strand synthesis at OL (red arrow). A, Strand-displacement model proposes single-stranded binding proteins (green spheres) bind the displaced H-strand during leading strand replication. B, Alternatively, the ribonucleotide incorporation throughout the lagging strand (RITOLS) model proposes portions of transcribed mitochondrial DNA bind the H-strand (green dotted line). [Powerpoint File]

Investigating the Transcriptional Control of Cardiovascular Development

Investigating the Transcriptional Control of Cardiovascular Development

Irfan S. Kathiriya*, Elphège P. Nora*, Benoit G. Bruneau

Studying cardiac regulatory elements. A, Left, Evolutionary constraints on some regulatory elements render them identifiable by comparative genomics, as exemplified by enhancers upstream of mouse Nkx2-5.86 Right, Combinations of specific chromatin features can reveal potential regulatory elements active in a given cell type. B, Left, Enhancer activity is classically tested by an ability of candidate elements to drive tissue- or stage-specific activity of a reporter. Middle, New technologies, such as SIF-seq,87 allow screening of large genomic neighborhoods for tissue-specific enhancers. Right, Genome Regulatory Organization Mapping with Integrated Transposons92 is a technology that can reveal integrated regulatory inputs exerted at a locus. [Powerpoint FIle]

Investigating the Transcriptional Control of Cardiovascular Development

Investigating the Transcriptional Control of Cardiovascular Development

Irfan S. Kathiriya*, Elphège P. Nora*, Benoit G. Bruneau

Molecular players for transcriptional regulation. A, Cis-regulatory elements containing DNA-binding sites are bound by transcription factors and (B) modulate the assembly of the preinitiation complex at promoters through (C) physical contacts driven by a 3-dimensional arrangement of chromatin, thereby acting as (D) a molecular platform between cellular signaling and gene activity. [Powerpoint File]

Molecular Regulation of Cardiomyocyte Differentiation

Molecular Regulation of Cardiomyocyte Differentiation

Sharon L. Paige, Karolina Plonowska, Adele Xu, Sean M. Wu

Regulation of cardiac mesoderm specification. Shown is a cross-section of an E7.5 mouse embryo detailing the signaling pathways that regulate cardiac specification within splanchnic mesoderm. Factors secreted by the adjacent endoderm that support cardiac mesoderm specification include fibroblast growth factor (FGF), bone morphogenetic protein (BMP), and sonic hedgehog (Shh). In addition, noncanonical Wnt ligands, such as Wnt11, expressed in splanchnic mesoderm also promote cardiac differentiation. Conversely, canonical Wnt ligands, including Wnt1, Wnt3a, and Wnt8, secreted from the overlying neuroectoderm, as well as BMP antagonists noggin and chordin secreted from the notochord inhibit cardiac mesoderm specification, thereby limiting the size of the cardiogenic fields. [Powerpoint File]

Molecular Regulation of Cardiomyocyte Differentiation

Molecular Regulation of Cardiomyocyte Differentiation

Sharon L. Paige, Karolina Plonowska, Adele Xu, Sean M. Wu

Schematic of cardiovascular lineage diversification. The specification of cardiomyocytes in the first heart field (FHF) and second heart field (SHF) is shown in the context of other cardiac cells that are also derived from a common cardiogenic mesoderm progenitor. In particular, Isl1 expression distinguishes the FHF and SHF. Comparison of action potentials for mature myocytes reveals the range of function generated from each heart field. *Developmental origin of the coronary endothelium is an active topic of investigation. Whereas some evidence points to partial contributions to the coronary endothelium from the epicardium,70,160 other sources, such as the endocardium161 and the sinus venosus,69 have also been reported. LV indicates left ventricle; and RV, right ventricle. [Powerpoint File]

Molecular Regulation of Cardiomyocyte Differentiation

Molecular Regulation of Cardiomyocyte Differentiation

Sharon L. Paige, Karolina Plonowska, Adele Xu, Sean M. Wu

Specification of chamber myocardium. The specification of cells to the chamber myocardium is modulated by Tbx5 and Tbx20 in tandem with more broadly expressed factors Nkx2-5 and Gata4. Tbx2 and Tbx3 suppress the expression of chamber myocardium–specific genes, resulting in low proliferation rate, slow conduction velocity, and poor contractibility characteristic to the primary myocardium. The primary myocardium phenotype becomes restricted to the atrioventricular canal (AVC) and proximal outflow tract (p-OFT). d-OFT indicates distal outflow tract; LA, left atrium; LV, left ventricle; and RV, right ventricle. [Powerpoint File]

Molecular Regulation of Cardiomyocyte Differentiation

Molecular Regulation of Cardiomyocyte Differentiation

Sharon L. Paige, Karolina Plonowska, Adele Xu, Sean M. Wu

Spatiotemporal regulation of trabeculation. The development of ventricular trabeculae is governed by signal transduction involving the endocardium, myocardium, and cardiac jelly. Pathways implicated in trabeculation are depicted in approximate chronological order of expression from left to right. Beginning with establishment of the cardiac jelly and endothelium, trabeculation progresses via cellular proliferation and migration and ends with degradation of the cardiac jelly. Factors involved in epigenetic mechanisms are underlined. BMP indicates bone morphogenetic protein; and VEGF, vascular endothelial growth factor. [Powerpoint File]