Gene network transitions in embryos and other fate-changing contexts involve combinations of transcription factors. A subset of fate-changing transcription factors act as pioneers; they scan and target nucleosomal DNA and initiate cooperative events that can open the local chromatin. However, a gap has remained in understanding how molecular interactions with the nucleosome contribute to the chromatin-opening phenomenon. Here we identified a short α-helical region, conserved among FOXA pioneer factors, that interacts with core histones and contributes to chromatin opening in vitro. The same domain is involved in chromatin opening in early mouse embryos for normal development. Thus, local opening of chromatin by interactions between pioneer factors and core histones promotes genetic programming.
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http://dx.doi.org/10.1038/s41588-020-0591-8 | DOI Listing |
Sci Adv
January 2025
Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Although lipid-derived acetyl-coenzyme A (CoA) is a major carbon source for histone acetylation, the contribution of fatty acid β-oxidation (FAO) to this process remains poorly characterized. To investigate this, we generated mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1, distal FAO enzyme) knockout macrophages. C-carbon tracing confirmed reduced FA-derived carbon incorporation into histone H3, and RNA sequencing identified diminished interferon-stimulated gene expression in the absence of ACAT1.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Purpose: The purpose of this study was to investigate the activated core kinases involved in the DNA damage responses (DDR) during ferroptosis of retinal pigment epithelial (RPE) cells in vitro and their regulatory effects on ferroptosis.
Methods: Ferroptosis was induced by erastin in induced RPE (iRPE) cells derived from human umbilical cord mesenchymal stem cells (hUCMSCs), hUCMSCs, and induced pluripotent stem cell-derived RPE (iPSC-RPE) cells. CCK8 was employed to measure the cell viability.
Proper histone gene expression is critical to cell viability and maintaining genomic integrity. Multiple histone genes organized into three genomic loci encode for replication coupled core and linker histones. Histone gene expression and transcript processing is orchestrated in the histone locus body (HLB) within the nucleus.
View Article and Find Full Text PDFMol Cell
January 2025
Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:
Cells integrate metabolic information into core molecular processes such as transcription to adapt to environmental changes. Chromatin, the physiological template of the eukaryotic genome, has emerged as a sensor and rheostat for fluctuating intracellular metabolites. In this review, we highlight the growing list of chromatin-associated metabolites that are derived from diverse sources.
View Article and Find Full Text PDFEur J Med Chem
December 2024
SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. Electronic address:
Histone deacetylase 6 (HDAC6) is a promising target for treating neurodegenerative disorders, several cancer types and viral infections. Unique among HDACs, the HDAC6 isoform possesses a zinc finger ubiquitin-binding domain (UBD) crucial for managing misfolded protein aggregates and facilitating viral infection. HDAC6 binds aggregated polyubiquitinated proteins through its UBD, mediating their transport to the aggresome and subsequent removal via autophagy.
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