February 15, 2013

The regulation of genes occurs at many levels, one of the first of which is physical access to a gene.  The way DNA is packaged may or may not allow transcription machinery from even getting to an area of the genome.  Understanding these modifications in each cell type and location is important, but difficult within a tissue or tumor of different cell types.  A recent paper tackles this problem with a new method.

Histones are proteins that package DNA to condense its size and to aid in gene regulation.  Histones can be modified in many different ways, and these modifications affect how accessible or inaccessible a certain region of the genome is to gene transcription.  Chromatin immunoprecipitation, the current technique to understand histone modifications at different gene sites, does not provide information on histone modifications of single cells within a complex environment of different cell types.  A recent paper describes a new technique that allows the visualization of histone modifications at single-cell resolution within a fixed tissue.  Using this technique, Gomez and colleagues tracked one specific histone modification, dimethylation of lysine 4 of histone H3 (H3K4me2) at the genetic loci for MYH11 in smooth muscle cells (SMC).  SMC-containing tissues contain other cell types, and even non-SMC tissues contain some SMCs due to vascularization.  In the images above, MYH11 H3K4me2 modifications (red, arrows) were found only in SMCs (green cells) in sections of human carotid artery tissue (DNA in blue).  Higher magnification images are bottom row.

Gomez, D., Shankman, L., Nguyen, A., & Owens, G. (2013). Detection of histone modifications at specific gene loci in single cells in histological sections Nature Methods, 10 (2), 171-177 DOI: 10.1038/nmeth.2332
Adapted by permission from Macmillan Publishers Ltd, copyright ©2013