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A shared characteristic of repressed genes within euchromatin and heterochromatin is the presence Heterochromatin Protein 1 (HP1) proteins. These were implicated in transcriptional repression as well as establishment and maintenance of heterochromatin silencing, although many of the key aspects are still poorly understood. To gain a better understanding of this family of proteins, I set up several test systems to analyze the contribution of HP1 proteins to chromatin transcription and architecture. Using defined in vitro assays, I have shown that HP1α specifically represses chromatin transcription and acetylation by inhibiting the p300 histone acetyl transferase. In a reporter gene system, HP1 hinders the coactivator function of p300. Furthermore, I provide evidence that HP1α ensures the hypoacetylated state of the pericentromeric heterochromatin in interphase, thus contributing to the silencing of the underlying DNA. In addition, I have determined the affinity of HP1 for mononucleosomes and provide evidence that it binds independent of the H3K9me3 modification with a low micro molar dissociation constant. Finally, my analyses suggest that two independent binding modes of HP1 to nucleosomes exist, that result in intra fiber compaction or inter fiber condensation of nucleosomal array, which might reflect different binding modes of HP1 in euchromatin and heterochromatin. Taken together, the results presented in this study provide answers for long standing questions of HP1 biology, namely the distinction between locally repressed genomic sequences vs. the globally silenced state within heterochromatin areas.
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Effects of heterochromatin protein 1 on chromatin transcription and architecture, Adrian Schomburg
- Sprache
- Erscheinungsdatum
- 2012
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- Titel
- Effects of heterochromatin protein 1 on chromatin transcription and architecture
- Sprache
- Englisch
- Autor*innen
- Adrian Schomburg
- Erscheinungsdatum
- 2012
- Einband
- Hardcover
- ISBN10
- 3866648596
- ISBN13
- 9783866648593
- Reihe
- Biological science
- Kategorie
- Skripten & Universitätslehrbücher
- Beschreibung
- A shared characteristic of repressed genes within euchromatin and heterochromatin is the presence Heterochromatin Protein 1 (HP1) proteins. These were implicated in transcriptional repression as well as establishment and maintenance of heterochromatin silencing, although many of the key aspects are still poorly understood. To gain a better understanding of this family of proteins, I set up several test systems to analyze the contribution of HP1 proteins to chromatin transcription and architecture. Using defined in vitro assays, I have shown that HP1α specifically represses chromatin transcription and acetylation by inhibiting the p300 histone acetyl transferase. In a reporter gene system, HP1 hinders the coactivator function of p300. Furthermore, I provide evidence that HP1α ensures the hypoacetylated state of the pericentromeric heterochromatin in interphase, thus contributing to the silencing of the underlying DNA. In addition, I have determined the affinity of HP1 for mononucleosomes and provide evidence that it binds independent of the H3K9me3 modification with a low micro molar dissociation constant. Finally, my analyses suggest that two independent binding modes of HP1 to nucleosomes exist, that result in intra fiber compaction or inter fiber condensation of nucleosomal array, which might reflect different binding modes of HP1 in euchromatin and heterochromatin. Taken together, the results presented in this study provide answers for long standing questions of HP1 biology, namely the distinction between locally repressed genomic sequences vs. the globally silenced state within heterochromatin areas.