inherited through cell division. This process is called epigenetic regulation. DNA methylation is reliably inherited through the action of maintenance methylases that modify the nascent DNA strand generated by replication. In mammalian cells, DNA methylation is the primary marker of transcriptionally silenced regions. Specialized proteins can recognize the marker and recruit histone deacetylases and methylases to re-establish the silencing. Nucleosome histone modifications could also be inherited during cell division, however, it is not clear whether it can work independently without the direction by DNA methylation. Gene-specific activation The two main tasks of transcription initiation are to provide RNA polymerase with an access to the promoter and to assemble general transcription factors with polymerase into a transcription initiation complex. Diverse mechanisms of initiating transcription by overriding inhibitory signals at the gene promoter have been identified. Eukaryotic genes have acquired extensive regulatory sequences that encompass a large number of regulator-binding sites and spread overall kilobases (sometimes hundreds of kilobases) from the promoter–-both upstream and downstream. The regulator binding sites are often clustered together into units called enhancers. Enhancers can facilitate highly cooperative action of several transcription factors (which constitute enhanceosomes). Remote enhancers allow transcription regulation at a distance. Insulators situated between enhancers and promoters help define the genes that an enhancer can or cannot influence. Eukaryotic transcriptional activators have separate DNA-binding and activating functions. Upon binding to its cis-element, an activator can recruit polymerase directly or recruit other factors needed by the transcriptional machinery. An activator can also recruit nucleosome modifiers that alter chromatin in the vicinity of the promoter and thereby help initiation. Multiple activators can work together, either by recruiting a common or two mutually dependent components of the transcriptional machinery, or by helping each other bind to their DNA sites. These interactions can synergize multiple signaling inputs and produce intricate transcriptional responses to address cellular needs. Gene-specific repression Eukaryotic transcription repressors share some of the mechanisms used by their prokaryotic counterparts. For example, by binding to a site on DNA that overlaps with the binding site of an activator, a repressor can inhibit binding of the activator. But more frequently, eukaryotic repressors inhibit the function of an activator by masking its activating domain, preventing its nuclear localization, promoting its degradation, or inactivating it through chemical modifications. Repressors can directly inhibit transcription initiation by binding to a site upstream of a promoter and interacting with the transcriptional machinery. Repressors can