Active VSG Expression Sites in Trypanosoma brucei Are Depleted of Nucleosomes

Abstract

In eukaryotes nuclear DNA is packaged into linear arrays of nucleosomes, which provides one of the main determinants of accessibility to DNA binding proteins (37,60,68,82). Nucleosomes consist of ϳ146 bp of DNA wrapped around a histone octamer composed of two copies each of histones H2A, H2B, H3, and H4 (44). The ability to change how DNA is packaged within nucleosomes allows variation in the accessibility of different DNA binding sites and permits fine modulation of promoter activity (33). Recently, there have been major advances in our understanding of how chromatin structure impacts the regulation of RNA polymerase II (Pol II) transcription units. New developments (72) have enabled the determination of the global organization of nucleosomes in organisms including budding yeast, Drosophila, and humans (3,35,36,48,71,83). These studies have shown evidence for nucleosome depletion at transcriptionally active regulatory regions, with the level of nucleosome occupancy inversely proportional to the rate of transcription initiation at the promoter (3, 36, 83). However, nucleosome remodeling at promoters does not always appear to be simply a consequence of transcriptional activity but is also thought to mechanistically regulate transcription through modulating the access of trans-acting factors (74).Our understanding of the role that chromatin structure plays in the regulation of RNA Pol I transcription has relatively lagged behind that of Pol II (reviewed in references 6, 21, and

Nucleosomes Are Depleted at the VSG Expression Site Transcribed by RNA Polymerase I in African Trypanosomes

“…As reported previously (19; also T. N. Siegel, personal communication) and by Stanne and Rudenko in this issue (29), H2A and H4 are also depleted at transcribed VSG genes, further suggesting that histone H3 content is a good indicator of nucleosome density.…”

Trypanosoma brucei TIF2 suppresses VSG switching by maintaining subtelomere integrity

“…The active BES differs from silent BESs in that it is actively transcribed by RNA polymerase I [59]. In addition, the active BES forms an open chromatin structure depleted of most nucleosomes, while silent BESs are packed with nucleosomes [60,61]. Our data suggest that the transcriptional status and/or the chromatin structure of the DSB site may influence the choice of DSB repair mechanism.…”

Transcription is initiated on silent variant surface glycoprotein expression sites despite monoallelic expression in Trypanosoma brucei

“…The mechanism controlling the selective activity of a single ES at a time is still unknown, although several factors have been found to be involved, such as differential chromatin/histone acetylation and methylation between active and inactive ESs (6-8); nucleosome depletion in the active ES (9,10); and the influence of various negative transcription modulators such as a histone methylase, a high-mobility group protein, histone H1, NLP (a nucleoplasm-like protein), a FACT subunit (a chromatin remodeler), a SWI/SNF (a chromatin remodeling factor), ORC1 and MCM-BP (proteins involved in the initiation of DNA replication), RAP1 (a telomere-binding protein), histone chaperones, or a lamin-like protein (8,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). However, no master ES regulator has been identified so far.…”