In this study, we investigated whether MGMT becomes silenced by promoter methylation in malignant pleural mesothelioma (MPM), an aggressive cancer of the pleura associated with a poor prognosis.
First, we have shown that the stably-integrated Ptetbi becomes silenced, provided it is inactive during development, and that high tTA/rtTA levels in neurons allow for Ptetbi un-silencing over time.
In the present manuscript, we report the discovery and functional characterization of a primate-specific noncoding RNA (FMR4) that becomes silenced as a result of the CGG expansion in the 5' UTR of FMR1 in fragile X syndrome.
Subsequent work from our laboratory indicates that CXCL12 expression becomes silenced in both breast and colorectal carcinomas via DNA promoter hypermethylation and that this epigenetic repression enhances metastasis [23], [24].
These genes define the subset C1a that acquires DNA methylation and becomes silenced.
In male mice the Stra8 promoter is selectively active in spermatogonia and their immediate descendants (preleptotene spermatocytes) [ 36- 39] before it becomes silenced upon further differentiation.
Therefore, it might also possible that ASIP is expressed in these MelSCs, and becomes silenced upon differentiation of the melanocytes in the epidermis.
Cells may become so transcriptionally inactive that p16 itself, although initially expressed, becomes silenced in some cells, growth stasis being maintained by silencing of genes required for cell proliferation.
If transgene silencing is transcription-dependent, then the nature of the promoter and enhancer elements in transgenes may also have a large bearing on whether or not a transgene becomes silenced.
Duplicated genes face three outcomes: non-functionalization (one copy becomes silenced); neo-functionalization (one copy acquires a novel, beneficial function, while the other copy retains the original function) or sub-functionalization (both copies become partially compromised by the accumulation of mutations) [ 35, 36, 21].
