A5000209329- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Plant Molecular Biology Research
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Virus-based gene therapy research
- Animal Genetics and Reproduction
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genomics, phytochemicals, and oxidative stress
- Neuropeptides and Animal Physiology
- RNA and protein synthesis mechanisms
- Neurobiology and Insect Physiology Research
- Protein Degradation and Inhibitors
- Glutathione Transferases and Polymorphisms
- Muscle Physiology and Disorders
- RNA regulation and disease
- Machine Learning in Bioinformatics
- Nuclear Issues and Defense
- interferon and immune responses
Stockholm University
2014-2024
Wenner-Gren Foundations
2002-2024
Institute of Developmental Physiology
2013
University of California, Berkeley
1999-2001
Uppsala University
1997-1999
University of Lisbon
1996
Nobel Foundation
1994
Karolinska Institutet
1994
Swedish Veterinary Agency
1992
Abstract The relationship between chromatin organization and gene regulation remains unclear. While disruption of domains domain boundaries can lead to misexpression developmental genes, acute depletion regulators genome has a relatively small effect on expression. It is therefore uncertain whether expression state drive or changes in facilitate cell-type-specific activation Here, using the dorsoventral patterning Drosophila melanogaster embryo as model system, we provide evidence for...
Abstract To maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of patterns upon mitotic exit is mediated, in part, by transcription factors (TF) bookmarking. However, the mechanisms and functions TF bookmarking early embryogenesis remain poorly understood. In this study, taking advantage naturally synchronized mitoses Drosophila embryos, we provide evidence that GAGA pioneer factor (GAF) acts...
Formation of tissue-specific transcriptional programs underlies multicellular development, including dorsoventral (DV) patterning the Drosophila embryo. This involves interactions between enhancers and promoters in a chromatin context, but how landscape influences transcription is not fully understood.
Here we show that the TATA-binding protein (TBP) is localized in nucleoplasm and nucleolus of mammalian cells, consistent with its known involvement transcription by RNA polymerase I, II, III. In actively growing TBP colocalizes upstream binding factor (UBF) I at sites rRNA transcription. During mitosis, when synthesis down-regulated, TBP-associated factors for (TAF(I)s), UBF, on chromosomal regions containing genes. Treatment cells a low concentration actinomycin D inhibits causes...
The COP9 signalosome (CSN) is an essential eight-subunit repressor of light-regulated development in Arabidopsis. This complex has also been identified animals, though its developmental role remains obscure. CSN subunits have implicated various cellular processes, suggesting a possible for the as integrator multiple signaling pathways. In order to elucidate function Drosophila model system previously established. Gel-filtration analysis with antibodies against 4, 5 and 7 revealed that these...
ABSTRACT The dorsal ectoderm of the Drosophila embryo is subdivided into different cell types by an activity gradient two TGFβ signaling molecules, Decapentaplegic (Dpp) and Screw (Scw). Patterning responses to this depend on a secreted inhibitor, Short gastrulation (Sog) newly identified transcriptional repressor, Brinker (Brk), which are expressed in neurogenic regions that abut ectoderm. Here we examine expression number Dpp target genes transgenic embryos contain ectopic stripes Dpp, Sog...
Previous studies have implicated histone deacetylation and chromatin condensation as critical mechanisms of transcription repression in yeast mammals. A specific deacetylase, Rpd3, interacts with a variety sequence-specific transcriptional repressors, including Mad-Max heterodimers members the nuclear receptor superfamily. Here, we present evidence that strong hypomorphic mutation Drosophila Rpd3 gene causes embryonic lethality pair-rule segmentation phenotype. The analysis number genes...
A correlation between histone acetylation and transcription has been noted for a long time, but little is known about what step(s) in the cycle influenced by acetylation. We have examined immediate transcriptional response to deacetylase (HDAC) inhibition, find that release of promoter-proximal paused RNA polymerase II (Pol II) into elongation stimulated, whereas initiation not. Although elevated globally HDAC less than 100 genes respond within 10 min. These are highly paused, strongly...
Maintenance of appropriate cell states involves epigenetic mechanisms, including Polycomb-group (PcG)-mediated transcriptional repression. While PcG proteins are known to induce chromatin compaction, how gain access DNA in compact achieve long-term silencing is poorly understood. Here, we show that the p300/CREB-binding protein (CBP) co-activator associated with two-thirds regions and required for occupancy at many these Drosophila mouse cells. CBP stabilizes RNA polymerase II (Pol II)...
CBP and the related p300 protein are widely used transcriptional co-activators in metazoans that interact with multiple transcription factors. Whether CBP/p300 occupies genome equally all factors or preferentially binds together some is not known. We therefore compared Drosophila melanogaster (nejire) ChIP–seq peaks regions bound by 40 different early embryos, we found high co-occupancy Rel-family Dorsal. Dorsal required for occupancy embryo, but only at where few other present. mutant...
Organismal development and cell differentiation critically depend on chromatin state transitions. However, certain developmentally regulated genes lack histone 3 lysine 9 27 acetylation (H3K9ac H3K27ac, respectively) 4 (H3K4) methylation, modifications common to most active genes. Here we describe a featuring unique 14 (H3K14ac) peaks in key tissue-specific Drosophila human cells. Replacing H3K14 demonstrates that is essential for expression of devoid canonical the embryonic gut larval wing...
Regulation of chromatin through histone acetylation is an important step in gene expression. The Gcn5 acetyltransferase part protein complexes, e.g., the SAGA complex, that interact with transcriptional activators, targeting enzyme to specific promoters and assisting recruitment basal RNA polymerase transcription machinery. Ada2 directly binds stimulates its catalytic activity. Drosophila contains two proteins, Ada2a (dAda2a) dAda2b. We have generated flies lack dAda2b, which a SAGA-like...
Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atro’s critical role development disease, relatively little is known about binding partners downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. identified 1300...
Abstract Histone acetyltransferase (HAT) complexes have been linked to activation of transcription. Reptin is a subunit different chromatin-remodeling complexes, including the TIP60 HAT complex. In Drosophila, also copurifies with Polycomb group (PcG) complex PRC1, which maintains genes in transcriptionally silent state. We demonstrate genetic interactions between reptin mutant flies and PcG mutants, resulting misexpression homeotic gene Scr. Genetic are not restricted PRC1 components, but...
Complex gene expression patterns in animal development are generated by the interplay of transcriptional activators and repressors at cis-regulatory DNA modules (CRMs). How work is not well understood, but often involves interactions with co-repressors. We isolated mutations brakeless a screen for maternal factors affecting segmentation Drosophila embryo. Brakeless, also known as Scribbler, or Master thickveins, nuclear protein unknown function. In embryos, we noted an expanded pattern...
Neuropeptide Y (NPY) has been implicated in depression, emotional processing and stress response. Part of this evidence originates from human single-nucleotide polymorphism (SNP) studies. In the present study, we report that a SNP rat Npy promoter (C/T; rs105431668) affects vitro transcription DNA–protein interactions. Genotyping studies showed C-allele rs105431668 is genetic model depression (Flinders sensitive line; FSL), while SNP's T-allele its controls resistant FRL). vivo experiments...
CREB-binding protein (CBP, also known as nejire) is a transcriptional co-activator that conserved in metazoans. CBP plays an important role embryonic development and cell differentiation mutations can lead to various diseases humans. In addition, the related p300 have successfully been used predict enhancers both humans flies when they occur with monomethylation of histone H3 on lysine 4 (H3K4me1). Here, we compare chromatin immunoprecipitation sequencing data from Drosophila S2 cells...
Abstract Gene overexpression through the targeting of transcription activation domains to regulatory DNA via catalytically defective Cas9 (dCas9) represents a powerful approach investigate gene function as well mechanisms control. To date, most efficient dCas9-based activator is Synergistic Activation Mediator (SAM) system whereby are directly fused dCas9 tethered MS2 loops engineered into gRNA. Here, we show that catalytic domain histone acetyltransferase CBP more potent than SAM at some...