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Publication : A high-resolution imaging approach to investigate chromatin architecture in complex tissues.

First Author  Linhoff MW Year  2015
Journal  Cell Volume  163
Issue  1 Pages  246-55
PubMed ID  26406379 Mgi Jnum  J:224900
Mgi Id  MGI:5689734 Doi  10.1016/j.cell.2015.09.002
Citation  Linhoff MW, et al. (2015) A High-Resolution Imaging Approach to Investigate Chromatin Architecture in Complex Tissues. Cell 163(1):246-55
abstractText  We present ChromATin, a quantitative high-resolution imaging approach for investigating chromatin organization in complex tissues. This method combines analysis of epigenetic modifications by immunostaining, localization of specific DNA sequences by FISH, and high-resolution segregation of nuclear compartments using array tomography (AT) imaging. We then apply this approach to examine how the genome is organized in the mammalian brain using female Rett syndrome mice, which are a mosaic of normal and Mecp2-null cells. Side-by-side comparisons within the same field reveal distinct heterochromatin territories in wild-type neurons that are altered in Mecp2-null nuclei. Mutant neurons exhibit increased chromatin compaction and a striking redistribution of the H4K20me3 histone modification into pericentromeric heterochromatin, a territory occupied normally by MeCP2. These events are not observed in every neuronal cell type, highlighting ChromATin as a powerful in situ method for examining cell-type-specific differences in chromatin architecture in complex tissues.
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