Unlocking the Mysteries of Chromatin Biology through Functional Epigenomics.

Autor: Ye Z; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.; Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts., Soshnev AA; Neuroscience, Developmental and Regenerative Biology, University of Texas, San Antonio, Texas., Soto-Feliciano Y; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.; Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts.
Jazyk: angličtina
Zdroj: Cancer research [Cancer Res] 2023 Dec 15; Vol. 83 (24), pp. 4010-4012.
DOI: 10.1158/0008-5472.CAN-23-3253
Abstrakt: In the ever evolving field of functional genomics, CRISPR-based screening technologies have become pivotal tools for elucidating gene function across various cell types. A recent study by Gilan and colleagues advances this technological frontier by introducing CRISPR-ChIP, a platform designed to investigate the complex dynamics of epigenetic regulation of chromatin. In proof-of-concept experiments, the authors demonstrate the potential of this tool to identify key molecular regulators of two major histone modifications associated with active transcription, H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 79 dimethylation (H3K79me2). They further unveiled a previously unknown functional partitioning of the H3K79-specific methyltransferase DOT1L into an oncogenic complex with MLL-AF9 and a native complex with MLLT10, which cooperatively regulate mixed lineage leukemia fusion protein (MLL-FP) target gene expression. This novel epigenomic approach integrates high-throughput CRISPR screening with chromatin immunoprecipitation-based direct readout of chromatin modifications in situ, offering a powerful tool to investigate the epigenetic regulatory layers across a diverse spectrum of biological processes and disease states.
(©2023 American Association for Cancer Research.)
Databáze: MEDLINE
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