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bioRxiv · 10.1101/2023.12.04.570024

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

Liu, S.·Zheng, P.·Wang, C. Y.·Jia, B. B.·Zemke, N. R.·Ren, B.·Zhuang, X.
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Abstract

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.

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Liu, S., Zheng, P., Wang, C. Y., Jia, B. B., Zemke, N. R., Ren, B., Zhuang, X.. 2023-12-05. Cell-type-specific 3D-genome organization and transcription regulation in the brain. https://doi.org/10.1101/2023.12.04.570024

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