A5068363917- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Reproductive Biology and Fertility
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Prenatal Screening and Diagnostics
- Protein Degradation and Inhibitors
- Genetic Syndromes and Imprinting
- Immunotherapy and Immune Responses
- Congenital heart defects research
- Plant Virus Research Studies
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2016-2025
National Institutes of Health
2016-2025
Salk Institute for Biological Studies
2009-2012
Howard Hughes Medical Institute
2011-2012
University of Pennsylvania
2001-2009
Johns Hopkins University
2004
Endogenous retroviruses (ERVs) constitute a substantial portion of mammalian genomes, and their retrotransposition activity helped to drive genetic variation, yet expression is tightly regulated prevent unchecked amplification. We generated series mouse mutants embryonic stem (ES) cell lines carrying "deletable" "rescuable" alleles the lysine-specific demethylase LSD1/KDM1A. In absence KDM1A, murine endogenous retrovirus MuERV-L/MERVL becomes overexpressed development arrests at...
Significance Transcriptional enhancers control cell-identity gene expression and thus determine cell identity. Enhancers are primed by histone H3K4 mono-/di-methyltransferase MLL4 before they activated H3K27 acetyltransferase p300. Here, we show that is dispensable for maintenance but essential fate transition using several model systems including embryonic stem (ESC) differentiation toward somatic cells reprogramming into ESC-like cells. Mechanistically, maintaining p300 binding on active...
In some mammals, notably humans, recombination occurs almost exclusively where the protein PRDM9 binds, whereas in vertebrates lacking an intact
The mechanisms of pathology for the family polyglutamine disease proteins are unknown; however, recently it was shown that several these inhibit transcription suggesting transcriptional repression may be a potential mechanism pathology. In present study we use cell transfections, in vitro binding, co-immunoprecipitations, and reporter assays to show protein, ataxin-3, interacts with major histone acetyltransferases cAMP-response-element binding protein (CREB)-binding p300, p300/CREB-binding...
Retroviruses have been invading mammalian germlines for millions of years, accumulating in the form endogenous retroviruses (ERVs) that account nearly one-tenth mouse and human genomes. ERVs are epigenetically silenced during development, yet cellular factors recognizing a sequence-specific manner remain elusive. Here we demonstrate ZFP809, member Krüppel-associated box zinc finger protein (KRAB-ZFP) family, initiates silencing via recruitment heterochromatin-inducing complexes. ZFP809...
TRIM28 is critical for the silencing of endogenous retroviruses (ERVs) in embryonic stem (ES) cells. Here, we reveal that an essential impact this process protection cellular gene expression early embryos from perturbation by cis -acting activators contained within these retroelements. In TRIM28-depleted ES cells, repressive chromatin marks at ERVs are replaced histone modifications typical active enhancers, stimulating transcription nearby genes, notably those harboring bivalent promoters....
Embryonic stem cells (ESCs) and induced pluripotent (iPSCs) efficiently generate all embryonic cell lineages but rarely extraembryonic types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse cells, yielding both strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features totipotent two-cell blastomeres. restricts acquisition expanded fate in it represses MERVL expression through transcriptional regulation, at least...
The Krüppel-associated box zinc finger protein (KRAB-ZFP) family diversified in mammals. majority of human KRAB-ZFPs bind transposable elements (TEs), however, since most TEs are inactive humans it is unclear whether emerged to suppress TEs. We demonstrate that many recently murine also TEs, including the active ETn, IAP, and L1 families. Using a CRISPR/Cas9-based engineering approach, we genetically deleted five large clusters target de-repressed, unleashing TE-encoded enhancers. Homozygous...
Histone acetylation by p300/CBP and PCAF coactivators is considered to be a key mechanism of chromatin modification transcriptional regulation. A multiprotein cellular complex, INHAT (inhibitor acetyltransferases), containing the Set/TAF-Iβ oncoprotein pp32 strongly inhibits HAT activity histone masking. Here we report that complex its subunits have overlapping but distinct inhibitory binding characteristics. We provide evidence suggesting can regulated physical association with other...
Somatic cell nuclear transfer has established that the oocyte contains maternal factors with epigenetic reprogramming capacity. Yet identity and function of these during gamete to embryo transition remains poorly understood. In C. elegans, LSD1/KDM1A enables this by removing H3K4me2 preventing transgenerational inheritance transcription patterns. Here we show loss in mice results embryonic arrest at 1-2 stage, arrested embryos failing undergo maternal-to-zygotic transition. This suggests is...
Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans other anthropoid primates remain poorly defined. Here, we show endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, turn, influences birth timing. Placental CRH subsequently prolonged were found two independent...
Linker histone H1 is a core chromatin component that binds to nucleosome particles and the linker DNA between nucleosomes. It has been implicated in compaction gene regulation anticipated play role higher-order genome structure. Here we have used combination of genome-wide approaches including methylation, modification DNase I hypersensitivity profiling as well Hi-C investigate impact reduced cellular levels embryonic stem cells on folding function.We find depletion changes epigenetic...