Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by augmented transforming growth factor-beta (TGF-beta) signaling leading to excessive extracellular matrix (ECM) deposition. The fibroblast-to-myofibroblast-transition (FMT) and metabolic reprogramming of lung fibroblasts (HLFs) are essential to IPF pathogenesis, yet the connection between nutrient metabolism and fibrogenesis remains poorly defined. The O-linked N-acetylglucosamine (O-GlcNAc) […]
Proteomic analysis of human leptomeningeal matrisome identifies changes in Alzheimer’s disease
The leptomeninges (arachnoid and pia) are the inner layers of the meninges that envelope the brain. They define the borders of the subarachnoid space (SAS) where cerebrospinal fluid (CSF) circulates. Leptomeninges act as the barrier tissue and contribute to fluid exchange and immune function of the brain. These processes are identified as key factors in […]
Rare RNA Polymerase II failure modes mark the cancer-driving genes most affected by epigenetic perturbation
RNA Polymerase II (Pol2) transcribes genes through a complex life cycle (initiation, pausing, elongation, co-transcriptional splicing, termination, and recycling). Chromatin immunoprecipitation of Pol2 before and after chemical perturbation has identified promoter-proximal accumulation (pausing) as a critical step in the transcription genome-wide. However, the full landscape of Pol2 responses has not been well characterized. Here, we […]
A conserved mechanism for regulation of mtDNA copy number in eukaryotes
Mitochondrial mass and mitochondrial DNA (mtDNA) copy number are coupled to metabolic demand at the cellular, tissue and organismal level, however, the molecular basis for homeostatic regulation of mtDNA is not understood. Here we show that mitochondria and mtDNA copy number are regulated by compartmentalisation of iron-sulfur (Fe-S) clusters, glutathione and cysteine, a mechanism we […]
A Toxic Tau-PFKFB3 Circuit Reduces F2,6BP Levels and Drives Neurodegeneration
Alzheimer’s disease (AD) and related dementias are progressive neurodegenerative disorders manifested by aggregation of Tau and Amyloid beta (Abeta). Emerging evidence suggests that metabolic dysregulation contributes to AD pathogenesis, yet how metabolic alterations interface with neuronal integrity remains unclear. Here, we identify dysfunction in PFKFB3-F2,6BP (fructose-2,6-bisphosphate) metabolic axis as a key feature of AD. We […]
Regulatory architecture controlling terminal differentiation of an interoceptive paraneuron in C. elegans
Interoceptive paraneurons are neuron-like cells located within internal epithelial cell surfaces that sense internal stimuli to evoke specific behavioral or physiological responses. The elucidation of terminal differentiation programs of paraneurons is expected to provide insights into how epithelial cells acquire neuron-like feature during development and possibly also over evolutionary time. We define here transcriptional programs […]
Shared binding sites for the chromosomal architectural protein Su(Hw) mediate physical interactions between Drosophila TAD boundaries
Loop extrusion has been clearly shown to be insufficient as a mechanism to explain TAD formation, leaving a large gap in our understanding of how the specificity of TAD boundary interactions and inter-TAD chromosomal interactions are determined. Many TAD binding proteins have been implicated in boundary interactions, including the gypsy transposon boundary binding protein Su(Hw). […]
A Toxic Tau-PFKFB3 Circuit Reduces F2,6BP Levels and Drives Neurodegeneration
Alzheimer’s disease (AD) and related dementias are progressive neurodegenerative disorders manifested by aggregation of Tau and Amyloid beta (Abeta). Emerging evidence suggests that metabolic dysregulation contributes to AD pathogenesis, yet how metabolic alterations interface with neuronal integrity remains unclear. Here, we identify dysfunction in PFKFB3-F2,6BP (fructose-2,6-bisphosphate) metabolic axis as a key feature of AD. We […]
A conserved mechanism for regulation of mtDNA copy number in eukaryotes
Mitochondrial mass and mitochondrial DNA (mtDNA) copy number are coupled to metabolic demand at the cellular, tissue and organismal level, however, the molecular basis for homeostatic regulation of mtDNA is not understood. Here we show that mitochondria and mtDNA copy number are regulated by compartmentalisation of iron-sulfur (Fe-S) clusters, glutathione and cysteine, a mechanism we […]
Regulatory architecture controlling terminal differentiation of an interoceptive paraneuron in C. elegans
Interoceptive paraneurons are neuron-like cells located within internal epithelial cell surfaces that sense internal stimuli to evoke specific behavioral or physiological responses. The elucidation of terminal differentiation programs of paraneurons is expected to provide insights into how epithelial cells acquire neuron-like feature during development and possibly also over evolutionary time. We define here transcriptional programs […]
Rare RNA Polymerase II failure modes mark the cancer-driving genes most affected by epigenetic perturbation
RNA Polymerase II (Pol2) transcribes genes through a complex life cycle (initiation, pausing, elongation, co-transcriptional splicing, termination, and recycling). Chromatin immunoprecipitation of Pol2 before and after chemical perturbation has identified promoter-proximal accumulation (pausing) as a critical step in the transcription genome-wide. However, the full landscape of Pol2 responses has not been well characterized. Here, we […]
Shared binding sites for the chromosomal architectural protein Su(Hw) mediate physical interactions between Drosophila TAD boundaries
Loop extrusion has been clearly shown to be insufficient as a mechanism to explain TAD formation, leaving a large gap in our understanding of how the specificity of TAD boundary interactions and inter-TAD chromosomal interactions are determined. Many TAD binding proteins have been implicated in boundary interactions, including the gypsy transposon boundary binding protein Su(Hw). […]