A5017645653- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- RNA Research and Splicing
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Chromatin Remodeling and Cancer
- Renal and related cancers
- Mechanisms of cancer metastasis
University of Pennsylvania
2015-2024
California Institute for Regenerative Medicine
2019-2024
Ludwig-Maximilians-Universität München
2011-2023
Amarantus Bioscience (United States)
2020
Translational Therapeutics (United States)
2019
Gene silencing by chromatin compaction is integral to establishing and maintaining cell fates. Trimethylated histone 3 lysine 9 (H3K9me3)-marked heterochromatin reduced in embryonic stem cells compared differentiated cells. However, the establishment dynamics of closed regions at protein-coding genes, embryologic development, remain elusive. We developed an antibody-independent method isolate map compacted from low-cell number samples. discovered high levels heterochromatin,...
Vertebrate embryos are derived from a transitory pool of pluripotent cells. By the process embryonic induction, these precursor cells assigned to specific fates and differentiation programs. Histone post-translational modifications thought play key role in establishment maintenance stable gene expression patterns underlying processes. While on level histone known change during differentiation, very little is about quantitative fluctuations bulk development. To investigate this issue we...
Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells differentiated somatic cell lineages. Repressive histone such as H3K9me3 or H3K27me3 have been investigated detail, but the role H4K20me3 development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2...
Mitosis is thought to be a period of transcriptional silence due the compact nature mitotic chromosomes and apparent exclusion RNA Pol II many transcription factors from chromatin. Yet accurate reactivation cell's specific gene expression program needed reestablish functional cell identity after mitosis. The majority studies on protein regulation localization during mitosis have relied extensively antibodies cross-linking-based approaches that are known artifactually exclude proteins Here we...
H4 lysine 20 dimethylation (H4K20me2) is the most abundant histone modification in vertebrate chromatin. It arises from sequential methylation of unmodified proteins by mono-methylating enzyme PR-SET7/KMT5A, followed conversion to dimethylated state SUV4-20H (KMT5B/C) enzymes. We have blocked deposition this mark depleting Xenopus embryos SUV4-20H1/H2 methyltransferases. In larval epidermis, results a severe loss cilia multiciliated cells (MCC), key component mucociliary epithelia. MCC...
Zygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these are initiated by local induction of regulatory genes through maternal signaling activities the wake zygotic genome activation (ZGA) at midblastula transition (MBT). These lay down body plan gastrulation and neurulation, accompanied massive changes chromatin structure, which increasingly constrain cellular plasticity. Here we report on developmental functions for Brahma related 1 (Brg1),...
Abstract H3K9me3-heterochromatin, established by lysine methyltransferases (KMTs) and compacted HP1 isoforms, represses alternative lineage genes DNA repeats. Our understanding of H3K9me3-heterochromatin stability is presently limited to individual domains We engineered Suv39h2 KO mouse embryonic stem cells degrade remaining two H3K9me3- KMTs within one hour found that both passive dilution active removal contribute H3K9me3 decay 12-24 hours. discovered four different rates across the genome...
SUMMARY Histone tails are subject to various post-translational modifications, which play a fundamental role in altering chromatin accessibility. Although they thought regulate progression through development, the impact of most abundant histone modification vertebrates, i.e., H4 lysine 20 dimethylation (H4K20m2), has remained largely elusive. H4K20m2 arises from sequential methylation new, unmodified proteins, incorporated into during DNA replication, by mono-methylating enzyme...