Cell-type-specific 3D-genome organization and transcription regulation in the brain.

Autor:	Liu S; Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA, USA., Zheng P; Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA, USA.; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA., Wang CY; Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA, USA., Jia BB; Bioinformatics and Systems Biology Graduate Program, Medical Scientist Training Program, University of California San Diego, La Jolla, CA, USA., Zemke NR; Department of Cellular and Molecular Medicine and Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Ren B; Department of Cellular and Molecular Medicine and Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Zhuang X; Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 05. Date of Electronic Publication: 2023 Dec 05.
DOI:	10.1101/2023.12.04.570024
Abstrakt:	3D organization of the genome plays a critical role in regulating gene expression. However, it remains unclear how chromatin organization differs among different cell types in the brain. Here we used genome-scale DNA and RNA imaging to investigate 3D-genome organization in transcriptionally distinct cell types in the primary motor cortex of the mouse brain. We uncovered a wide spectrum of differences in the nuclear architecture and 3D-genome organization among different cell types, ranging from the physical size of the cell nucleus to the active-inactive chromatin compartmentalization and radial positioning of chromatin loci within the nucleus. These cell-type-dependent variations in nuclear architecture and chromatin organization exhibited strong correlation with both total transcriptional activity of the cell and transcriptional regulation of cell-type-specific marker genes. Moreover, we found that the methylated-DNA-binding protein MeCP2 regulates transcription in a divergent manner, depending on the nuclear radial positions of chromatin loci, through modulating active-inactive chromatin compartmentalization. Competing Interests: Competing interests: X.Z. is an inventor of patents applied for by Harvard University related MERFISH and a co-founder and consultant of Vizgen, Inc. B.R. is a co-founder and consultant of Arima Genomics, and a co-founder of Epigenome Technologies, Inc.
Databáze:	MEDLINE
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