Genome-wide analysis of dMi-2 binding sites

ATP-dependent chromatin remodelers regulate gene expression. The actions of chromatin remodelers on the nucleosome removal and assembly, the histone variants exchange and the modifications of the nucleosome array modify the accessibility of the transcriptional machinery to DNA. Transcription is also...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: Mathieu, Eve-Lyne
Beteiligte: Brehm, Alexander (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2013
Molekularbiologie und Tumorforschung
Ausgabe:http://dx.doi.org/10.17192/z2013.0665
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Zusammenfassung:ATP-dependent chromatin remodelers regulate gene expression. The actions of chromatin remodelers on the nucleosome removal and assembly, the histone variants exchange and the modifications of the nucleosome array modify the accessibility of the transcriptional machinery to DNA. Transcription is also influenced by the chromatin context. Indeed, the presence of transcription factors, nucleosome-depleted regions and histone modifications, facilitate the recruitment of specific histone modifying enzymes, chromatin modifying enzymes and chromatin remodelers. Thus, several chromatin features influence the transcription outcome. The ATP-dependent chromatin remodeler dMi-2 is typically associated with transcription repression, but its implication in active transcription has also been reported. The dMi-2 binding sites on polytene chromosomes suggest that dMi-2 binds mainly in open chromatin regions. However, the resolution of polytene staining is approximate and does not give any information about the chromatin context surrounding dMi-2. Thus, the genome-wide dMi-2 binding sites have been identified by ChIP-sequencing and correlated with existing data of histone modifications, RNA polymerase II, nucleosome-depleted regions, transcription, transcription factors and chromatin states. All in all, dMi-2 is located in open chromatin regions and in vicinity of developmental genes. Although dMi-2 mainly represses the expression of its associated genes, it binds close to features linked to active transcription and it is enriched in promoters and in potential regulatory regions. Upon heat shock, the inducible hsp70 gene is actively transcribed, and dMi-2 is important for its expression. To investigate the factors influencing the recruitment of dMi-2 in a context of active transcription, the dMi-2 genome-wide binding sites in un-induced and heat shock conditions have been identified by ChIP-sequencing. dMi-2 is selectively enriched on 7 hsp genes. The chromatin features associated to the hsp70 promoter or a nucleosome-depleted region does not suffice to recruit dMi-2. Moreover, a strong transcription is not sufficient to recruit dMi-2, even though its recruitment on the heat shock genes is transcription dependent. Notably, dMi-2 distribution encompasses the gene body and extent beyond the polyadenylation site of the heat shock genes. Thus, the results suggest that dMi-2 follow the transcriptional activity.
DOI:http://dx.doi.org/10.17192/z2013.0665