Abstract:
:We recently described two opposing states of transcriptional competency. One is termed 'competent' whereby a gene is capable of responding to trans-acting transcription factors of the cell, such that it is active if appropriate transcriptional activators are present, though it can also be silent if activators are absent or repressors are present. The other is termed 'occluded' whereby a gene is silenced by cis-acting, chromatin-based mechanisms in a manner that blocks it from responding to trans-acting factors, such that it is silent even when activators are present in the cellular milieu. We proposed that gene occlusion is a mechanism by which differentiated cells stably maintain their phenotypic identities. Here, we describe chromatin analysis of occluded genes. We found that DNA methylation plays a causal role in maintaining occlusion for a subset of occluded genes. We further examined a variety of other chromatin marks typically associated with transcriptional silencing, including histone variants, covalent histone modifications and chromatin-associated proteins. Surprisingly, we found that although many of these marks are robustly linked to silent genes (which include both occluded genes and genes that are competent but silent), none is linked specifically to occluded genes. Although the observation does not rule out a possible causal role of these chromatin marks in occlusion, it does suggest that these marks might be secondary effect rather than primary cause of the silent state in many genes.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Lee JH,Gaetz J,Bugarija B,Fernandes CJ,Snyder GE,Bush EC,Lahn BTdoi
10.1093/hmg/ddp188subject
Has Abstractpub_date
2009-07-15 00:00:00pages
2567-74issue
14eissn
0964-6906issn
1460-2083pii
ddp188journal_volume
18pub_type
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