AI Article Synopsis
Article Abstract
Chromatin modifications regulate genome function by recruiting proteins to the genome. However, the protein composition at distinct chromatin modifications has yet to be fully characterized. In this study, we used natural protein domains as modular building blocks to develop engineered chromatin readers (eCRs) selective for DNA methylation and histone tri-methylation at H3K4, H3K9 and H3K27 residues. We first demonstrated their utility as selective chromatin binders in living cells by stably expressing eCRs in mouse embryonic stem cells and measuring their subnuclear localization, genomic distribution and histone-modification-binding preference. By fusing eCRs to the biotin ligase BASU, we established ChromID, a method for identifying the chromatin-dependent protein interactome on the basis of proximity biotinylation, and applied it to distinct chromatin modifications in mouse stem cells. Using a synthetic dual-modification reader, we also uncovered the protein composition at bivalently modified promoters marked by H3K4me3 and H3K27me3. These results highlight the ability of ChromID to obtain a detailed view of protein interaction networks on chromatin.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289633 | PMC |
| http://dx.doi.org/10.1038/s41587-020-0434-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genomic and transcriptomic profiling of radioresistant prostate and head and neck cancers implicate a BAHD1-dependent modification of DNA damage at the heterochromatin.
Cell Death Dis
December 2024
Division of Medical Sciences, National Cancer Centre Singapore, 30 Hospital Blvd, 168583, Singapore, Singapore.
Radiotherapy is an integral modality in treating human cancers, but radioresistance remains a clinical challenge due to the involvement of multiple intrinsic cellular and extrinsic tumour microenvironment factors that govern radiosensitivity. To study the intrinsic factors that are associated with cancer radioresistance, we established 4 radioresistant prostate (22Rv1 and DU145) and head and neck cancer (FaDu and HK1) models by irradiating their wild-type parentals to 90 Gy, mimicking the fractionated radiotherapy schema that is often using in the clinic, and performed whole exome and transcriptome sequencing of the radioresistant and wild-type models. Comparative genomic analyses detected the enrichment of mismatch repair mutational signatures (SBS6, 14, 15, 20) across all the cell lines and several non-synonymous single nucleotide variants involved in pro-survival pathways.
View Article and Find Full Text PDFT lymphocyte plasticity in chronic inflammatory diseases: The emerging role of the Ikaros family as a key Th17-Treg switch.
Autoimmun Rev
December 2024
APC Microbiome Ireland, University College Cork, Ireland; College of Medicine and Health, University College Cork, Ireland.
T helper (Th) 17 and regulatory T (Treg) cells are highly plastic CD4 Th cell subsets, being able not only to actively adapt to their microenvironment, but also to interconvert, acquiring mixed identity markers. These phenotypic changes are underpinned by transcriptional control mechanisms, chromatin reorganization events and epigenetic modifications, that can be hereditable and stable over time. The Ikaros family of transcription factors have a predominant role in T cell subset specification through mechanisms of transcriptional program regulation that enable phenotypical diversification.
View Article and Find Full Text PDFCHD6 eviction of promoter nucleosomes maintains housekeeping transcriptional program in prostate cancer.
Mol Ther Nucleic Acids
December 2024
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
CHD6, a member of the chromodomain helicase DNA-binding protein family, has been implicated in various diseases and tumors. However, its precise binding model of CHD6 on regulatory functional genes remains poorly understood. In this study, we discovered sharp peaks of CHD6, as the first member of CHD family for housekeeping process, binding only to the promoter region of genes in the C4-2 cell line.
View Article and Find Full Text PDFChromatin Organization during Early Development.
DNA (Basel)
March 2024
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Embryogenesis is characterized by dynamic chromatin remodeling and broad changes in chromosome architecture. These changes in chromatin organization are accompanied by transcriptional changes, which are crucial for the proper development of the embryo. Several independent mechanisms regulate this process of chromatin reorganization, including segregation of chromatin into heterochromatin and euchromatin, deposition of active and repressive histone modifications, and the formation of 3D chromatin domains such as TADs and LADs.
View Article and Find Full Text PDFUnlabelled: Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting epigenetic regulators using our dual reporter system, we found that inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation and anti-tumor activity. Comprehensive biochemical, chemical, and genetic experiments revealed that on-target blockade of the HDAC1/2 catalytic domain mediated the differentiated phenotype.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!