Chromatin dynamics at DNA replication, transcription and repair

Abstract

During DNA replication, transcription and DNA repair in eukaryotes, the cellular machineries performing these tasks need to gain access to the DNA that is packaged into chromatin in the nucleus. Chromatin is a dynamic structure that modulates the access of regulatory factors to the genetic material. A precise coordination and organization of events in opening and closing of the chromatin is crucial to ensure that the correct spatial and temporal epigenetic code is maintained within the eukaryotic genome. This review will summarize the current knowledge of how chromatin remodeling and histone modifying complexes cooperate to break and remake chromatin during nuclear processes on the DNA template.

Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60

“…As a consequence of chromatin compaction, chromatin is generally repressive and has to be opened up to allow access for transcription, replication, recombination and repair (Ehrenhofer-Murray, 2004). In the next paragraphs, it will be discussed how dynamic changes in chromatin structure can be achieved.…”

“…Histones are small basic proteins and can carry posttranslational modifications, namely acetylation, methylation, phosphorylation, ubiquitylation, sumoylation and ADPribosylation (Ehrenhofer-Murray, 2004). The majority of these modifications are positioned at the N-terminal tails of histones, with the exception of ubiquitylation, which is found at the C-terminal part of H2A and H2B.…”

“…HATs are generally thought to activate gene transcription by loosening chromatin compaction and by creating binding sites for the bromodomain moieties of transcription factor complexes through lysine acetylation, therefore facilitating access of the transcriptional machinery to the DNA (Ehrenhofer-Murray, 2004). In agreement with this notion, the Tip60 complex is recruited to promoters by DNA-binding factors and acts as a transcriptional co-activator in several contexts.…”

Histone deacetylase inhibitors and genomic instability

“…Since the identification of the first histone acetyltransferases (HATs) and histone deacetylases (HDACs) and their respective functions in regulation of transcription in the mid-90s [3][4][5][6][7][8][9], interest in previously overlooked protein post-translational modifications has been renewed [10][11][12][13]. There is now a growing body of evidence that protein acetylation is involved in a large number of cell signaling pathways, reminiscent of protein phosphorylation [14].…”

Gene splice sites correlate with nucleosome positions

“…Nucleosomes, the building blocks of eukaryotic chromatin, play a key role in the organization of the overall chromatin structure and participate in regulated gene functioning [Anderson and Widom 2000;Ehrenhofer-Murray 2004]. Chromatin can also be involved in protection of functionally important sequence sites.…”