Crystal structure of an ENT domain from Trypanosoma brucei

Mi, Juan; Xiao, Yang; Zhang, Jiahai; Zhang, Xuecheng; Xu, Chao; Liao, Shanhui; Tu, Xiaoming

doi:10.1016/j.bbrc.2018.09.167

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…LmxM.24.0530, which was enriched almost 14-fold, is predicted to contain an EMSY N-Terminal Domain (ENT). EMSY is a protein implicated in DNA repair, transcription and human tumorigenesis 47 , 48 . LmxM.24.1230 was identified as 7-fold enriched, and domain searching identified a putative acetyltransferase in the N-terminal region as well as PHD-Zinc Finger domain.…”

Section: Resultsmentioning

confidence: 99%

Bromodomain factor 5 is an essential regulator of transcription in Leishmania

et al. 2022

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Leishmania are unicellular parasites that cause human and animal diseases. Like other kinetoplastids, they possess large transcriptional start regions (TSRs) which are defined by histone variants and histone lysine acetylation. Cellular interpretation of these chromatin marks is not well understood. Eight bromodomain factors, the reader modules for acetyl-lysine, are found across Leishmania genomes. Using L. mexicana, Cas9-driven gene deletions indicate that BDF1–5 are essential for promastigotes. Dimerisable, split Cre recombinase (DiCre)-inducible gene deletion of BDF5 show it is essential for both promastigotes and murine infection. ChIP-seq identifies BDF5 as enriched at TSRs. XL-BioID proximity proteomics shows the BDF5 landscape is enriched for BDFs, HAT2, proteins involved in transcriptional activity, and RNA processing; revealing a Conserved Regulators of Kinetoplastid Transcription (CRKT) Complex. Inducible deletion of BDF5 causes global reduction in RNA polymerase II transcription. Our results indicate the requirement of Leishmania to interpret histone acetylation marks through the bromodomain-enriched CRKT complex for normal gene expression and cellular viability.

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Section: Resultsmentioning

confidence: 99%

Bromodomain factor 5 is an essential regulator of transcription in Leishmania

et al. 2022

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“…We also note that Tb927.3.4140 displays similarity to Poly ADP Ribose Polymerase (PARP; Supplemental Table S5), suggesting that ribosylation might contribute to TSR definition by promoting chromatin decompaction as seen upon Drosophila heat shock puff induction (Sawatsubashi et al, 2004; and at some mammalian enhancers-promoter regions (Benabdallah et al, 2019). Tb927.11.5230 contains an EMSY ENT domain whose structure has been determined (Mi et al, 2018; Supplemental Table S5); such domains are present in several chromatin regulators. Tb927.4.2340 exhibits similarity to the C-terminal region of the vertebrate TFIID TAF1 subunit (Supplemental Table S5).…”

Section: Bdf3 (Class I) Bdf5 (Class Ii) and Hat2 (Class Ii)mentioning

confidence: 97%

A systematic analysis of Trypanosoma brucei chromatin factors identifies novel protein interaction networks associated with sites of transcription initiation and termination

et al. 2021

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Nucleosomes composed of histones are the fundamental units around which DNA is wrapped to form chromatin. Transcriptionally active euchromatin or repressive heterochromatin is regulated in part by the addition or removal of histone post-translational modifications (PTMs) by ‘writer’ and ‘eraser’ enzymes, respectively. Nucleosomal PTMs are recognised by a variety of ‘reader’ proteins which alter gene expression accordingly. The histone tails of the evolutionarily divergent eukaryotic parasite Trypanosoma brucei have atypical sequences and PTMs distinct from those often considered universally conserved. Here we identify 65 predicted readers, writers and erasers of histone acetylation and methylation encoded in the T. brucei genome and, by epitope tagging, systemically localize 60 of them in the parasite’s bloodstream form. ChIP-seq demonstrated that fifteen candidate proteins associate with regions of RNAPII transcription initiation. Eight other proteins exhibit a distinct distribution with specific peaks at a subset of RNAPII transcription termination regions marked by RNAPIII-transcribed tRNA and snRNA genes. Proteomic analyses identified distinct protein interaction networks comprising known chromatin regulators and novel trypanosome-specific components. Several SET-domain and Bromo-domain protein networks suggest parallels to RNAPII promoter-associated complexes in conventional eukaryotes. Further, we identify likely components of TbSWR1 and TbNuA4 complexes whose enrichment coincides with the SWR1-C exchange substrate H2A.Z at RNAPII transcriptional start regions. The systematic approach employed provides detail of the composition and organization of the chromatin regulatory machinery in Trypanosoma brucei and establishes a route to explore divergence from eukaryotic norms in an evolutionarily ancient but experimentally accessible eukaryote.

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“…LmxM.24.0530, which was enriched almost 14-fold, is predicted to contain an EMSY N-Terminal Domain (ENT). EMSY is a protein implicated in DNA repair, transcription and human tumorigenesis 57,58 . LmxM.24.1230 was identified as 7-fold enriched, and domain searching identified a putative acetyltransferase in the N-terminal region as well as PHD-Zinc Finger domain.…”

Section: Bromodomain Factors In Leishmaniamentioning

confidence: 99%

Bromodomain factor 5 is an essential transcriptional regulator of the Leishmania genome

Jones

Geoghegan

Moore

et al. 2021

Preprint

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Leishmania are unicellular parasites that cause human and animal disease. Alongside other organisms in kinetoplastida, they have evolved an unusual genome architecture that requires all RNA polymerase II transcribed genes to be expressed constitutively, with transcriptional start regions denoted by histone variants and histone lysine acetylation. However, the way these chromatin marks are interpreted by the cell is not understood. Seven predicted bromodomain factors (BDF1-7), the reader modules for acetyl-lysine, were identified across Leishmania genomes. Using L. mexicana as a model, Cas9-driven gene deletions indicate that BDF1-5 are essential for promastigote survival, whilst DiCre inducible gene deletion of the dual bromodomain factor BDF5 identified it to be essential for both promastigotes and amastigotes. ChIP-seq assessment of BDF5s genomic distribution revealed it as highly enriched at transcriptional start sites. Using an optimised proximity proteomic and phosphoproteomic technique, XL-BioID, we defined the BDF5-proximal environment to be enriched for other bromodomain factors, histone acetyltransferase 2, and proteins essential for transcriptional activity and RNA processing. Inducible deletion of BDF5, led to a disruption of pol II transcriptional activity and global defects in gene expression. Our results indicate the requirement of Leishmania to interpret histone acetylation marks for normal levels of gene expression and thus cellular viability.

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Crystal structure of an ENT domain from Trypanosoma brucei

Cited by 3 publications

References 26 publications

Bromodomain factor 5 is an essential regulator of transcription in Leishmania

Bromodomain factor 5 is an essential regulator of transcription in Leishmania

A systematic analysis of Trypanosoma brucei chromatin factors identifies novel protein interaction networks associated with sites of transcription initiation and termination

Bromodomain factor 5 is an essential transcriptional regulator of the Leishmania genome

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