Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.
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http://dx.doi.org/10.1038/s41467-021-23922-2 | DOI Listing |
Cell Rep
January 2025
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Chromatin regulatory proteins are expressed broadly and assumed to exert the same intrinsic function across cell types. Here, we report that 14 chromatin regulators undergo evolutionary-conserved neuron-specific splicing events involving microexons. Among them are two components of a histone demethylase complex: LSD1 H3K4 demethylase and the H3K4me0-reader PHF21A.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Molecular Genetics and Genomics, New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA.
Gene expression is regulated by chromatin DNA methylation and other features, including histone post-translational modifications (PTMs), chromatin remodelers and transcription factor occupancy. A complete understanding of gene regulation will require the mapping of these chromatin features in small cell number samples. Here we describe a novel genome-wide chromatin profiling technology, named as Nicking Enzyme Epitope targeted DNA sequencing (NEED-seq).
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, China.
Tryptophan participates in important life activities and is involved in various metabolic processes. The indole and aromatic binuclear ring structure in tryptophan can engage in diverse interactions, including π-π, π-alkyl, hydrogen bonding, cation-π, and CH-π interactions with other side chains and protein targets. These interactions offer extensive opportunities for drug development.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
The spatial organization of the genome plays a critical role in regulating gene expression, cellular differentiation, and genome stability. This review provides an in-depth examination of the methodologies, computational tools, and frameworks developed to map the three-dimensional (3D) architecture of the genome, focusing on both ligation-based and ligation-free techniques. We also explore the limitations of these methods, including biases introduced by restriction enzyme digestion and ligation inefficiencies, and compare them to more recent ligation-free approaches such as Genome Architecture Mapping (GAM) and Split-Pool Recognition of Interactions by Tag Extension (SPRITE).
View Article and Find Full Text PDFAm J Hum Genet
January 2025
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, USA. Electronic address:
cis-regulatory elements (CREs) control gene transcription dynamics across cell types and in response to the environment. In asthma, multiple immune cell types play an important role in the inflammatory process. Genetic variants in CREs can also affect gene expression response dynamics and contribute to asthma risk.
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