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Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin
The kinetochore directs the separation of chromosomes and is assembled at a special region of the chromosome—the centromere. DNA is wrapped around particles called nucleosomes, which contain histone proteins. The nucleosomes at centromeres are specialized, and contain the centromere-specific histone CENP-A. CENP-A nucleosomes form the platform upon which the kinetochore is built. Thus, CENP-A and centromere function go hand-in-hand. How the cell ensures that CENP-A is deposited at centromeres and not elsewhere is not well understood. We investigated the role that DNA sequence plays in defining centromere function in fission yeast. Our observations suggest that it is not the DNA sequence per se that is important for attracting CENP-A, but rather, the particular environment that the sequence creates. During transcription of centromeric DNA, RNA polymerase (RNAPII) appears to get stuck or stalled. Particular proteins—such as TFIIS and Ubp3—are known to help restart RNAPII so it can continue transcribing. We found that when cells lack Ubp3 or TFIIS, CENP-A becomes deposited on centromere sequences. We propose that persistent stalling of RNAPII on centromere DNA attracts factors that help deposit CENP-A. This study highlights the influence of DNA sequence in creating an attractive environment for CENP-A assembly.
Vyšlo v časopise: Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1004986
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004986Souhrn
The kinetochore directs the separation of chromosomes and is assembled at a special region of the chromosome—the centromere. DNA is wrapped around particles called nucleosomes, which contain histone proteins. The nucleosomes at centromeres are specialized, and contain the centromere-specific histone CENP-A. CENP-A nucleosomes form the platform upon which the kinetochore is built. Thus, CENP-A and centromere function go hand-in-hand. How the cell ensures that CENP-A is deposited at centromeres and not elsewhere is not well understood. We investigated the role that DNA sequence plays in defining centromere function in fission yeast. Our observations suggest that it is not the DNA sequence per se that is important for attracting CENP-A, but rather, the particular environment that the sequence creates. During transcription of centromeric DNA, RNA polymerase (RNAPII) appears to get stuck or stalled. Particular proteins—such as TFIIS and Ubp3—are known to help restart RNAPII so it can continue transcribing. We found that when cells lack Ubp3 or TFIIS, CENP-A becomes deposited on centromere sequences. We propose that persistent stalling of RNAPII on centromere DNA attracts factors that help deposit CENP-A. This study highlights the influence of DNA sequence in creating an attractive environment for CENP-A assembly.
Zdroje
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