RT Journal
A1 Looney, Timothy J.
A1 Zhang, Li
A1 Chen, Chih-Hsin
A1 Lee, Jae Hyun
A1 Chari, Sheila
A1 Mao, Frank Fuxiang
A1 Pelizzola, Mattia
A1 Zhang, Lu
A1 Lister, Ryan
A1 Baker, Samuel W.
A1 Fernandes, Croydon J.
A1 Gaetz, Jedidiah
A1 Foshay, Kara M.
A1 Clift, Kayla L.
A1 Zhang, Zhenyu
A1 Li, Wei-Qiang
A1 Vallender, Eric J.
A1 Wagner, Ulrich
A1 Qin, Jane Yuxia
A1 Michelini, Katelyn J.
A1 Bugarija, Branimir
A1 Park, Donghyun
A1 Aryee, Emmanuel
A1 Stricker, Thomas
A1 Zhou, Jie
A1 White, Kevin P.
A1 Ren, Bing
A1 Schroth, Gary P.
A1 Ecker, Joseph R.
A1 Xiang, Andy Peng
A1 Lahn, Bruce T.
T1 Systematic mapping of occluded genes by cell fusion reveals prevalence and stability of cis-mediated silencing in somatic cells
JF Genome Research 
JO Genome Research 
YR 2014 
FD February 01 
VO 24 
IS 2 
SP 267 
OP 280 
DO 10.1101/gr.143891.112 
UL http://genome.cshlp.org/content/24/2/267.abstract 
AB Both diffusible factors acting in trans and chromatin components acting in cis are implicated in gene regulation, but the extent to which either process causally determines a cell's transcriptional identity is unclear. We recently used cell fusion to define a class of silent genes termed “cis-silenced” (or “occluded”) genes, which remain silent even in the presence of trans-acting transcriptional activators. We further showed that occlusion of lineage-inappropriate genes plays a critical role in maintaining the transcriptional identities of somatic cells. Here, we present, for the first time, a comprehensive map of occluded genes in somatic cells. Specifically, we mapped occluded genes in mouse fibroblasts via fusion to a dozen different rat cell types followed by whole-transcriptome profiling. We found that occluded genes are highly prevalent and stable in somatic cells, representing a sizeable fraction of silent genes. Occluded genes are also highly enriched for important developmental regulators of alternative lineages, consistent with the role of occlusion in safeguarding cell identities. Alongside this map, we also present whole-genome maps of DNA methylation and eight other chromatin marks. These maps uncover a complex relationship between chromatin state and occlusion. Furthermore, we found that DNA methylation functions as the memory of occlusion in a subset of occluded genes, while histone deacetylation contributes to the implementation but not memory of occlusion. Our data suggest that the identities of individual cell types are defined largely by the occlusion status of their genomes. The comprehensive reference maps reported here provide the foundation for future studies aimed at understanding the role of occlusion in development and disease.