TFIIIC-based chromatin insulators through eukaryotic evolution

Sizer, Rebecca E.; Chahid, Nisreen; Butterfield, Sienna P.; Donze, David; Bryant, Nia J.; White, Robert J.

doi:10.1016/j.gene.2022.146533

Cited by 8 publications

(10 citation statements)

References 157 publications

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“…Instead, authors show that histone methylations ( i.e., H3K9me3) primarily inhibit RNAPIII transcription at SINEs (Varshney et al, 2015). In parallel, Sizer and colleagues exemplifies several TFIIIC, TFIIIB and RNAPIII-bound tRNA genes located in CpG islands (Sizer et al, 2022). Furthermore, C. elegans TFIIIC pauses independently of RNAPIII recruitment at repetitive tRNA-like pseudogenes and SINEs enriched in H3K9me2, an heterochromatic mark found in the SYY cluster (Stutzman, et al, 2020; Hummel et al, 2020; Hummel and Liu, 2022).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional reactivation of the tRNA^Ser/tRNA^Tyrgene cluster inArabidopsis thalianaroot tip (V2)

Hummel,

Kumari,

Hua

et al. 2023

Preprint

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Plants retain an exhaustive tRNA gene repertoire in their nuclear genome. How important are these individuals, how exactly plants orchestrate their usage, and for what purposes, is poorly understood.Arabidopsis thalianachromosome 1 holds a cluster of tandemly repeated tRNASerand tRNATyrgenes (SYY cluster). They intersect with constitutive heterochromatin and are transcriptionally silenced. Here, we resolve the tissular expression pattern of this cluster along seedling establishment. We show the root cap columella and few adjacent lateral root cap cells to be the main sources of SYY cluster tRNAs. The transcriptional reactivation of this genomic region occurs there although elevated DNA methylation levels. Furthermore, we evidence that these cells are able to accumulate high levels of a transgenic EXTENSIN rich in serine and tyrosine, and that the CRISPR/Cas9 deletion of the SYY cluster alters such phenomenon. Altogether, our work sheds light on pioneering evidence of a developmental and cell-specific expression program for a plant tRNA gene.

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Section: Discussionmentioning

confidence: 99%

Transcriptional reactivation of the tRNA^Ser/tRNA^Tyrgene cluster inArabidopsis thalianaroot tip (V2)

Hummel,

Kumari,

Hua

et al. 2023

Preprint

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“…Deregulation of the Pol III transcription apparatus was reported in various cancers [reviewed in (10)], and increased expression and protein levels of TFIIIC subunits were found in ovarian cancers (11) and during tumoral transformation (12). Independently of its role in recruiting Pol III to its target genes, TFIIIC recognizes "extra TFIIIC" (ETC) sites in various eukaryotes (13)(14)(15) and functions in genome organization by acting as a chromatin insulator (16,17) and via interaction with the architectural proteins cohesin and condensin (18)(19)(20)(21). TFIIIC also has histone acetylation activity and, together with the insulator protein CCCTC-binding factor, was shown to mediate long-range chromatin looping (22,23).…”

Section: Introductionmentioning

confidence: 99%

Structural insights into human TFIIIC promoter recognition

Seifert-Davila,

Girbig,

Hauptmann

et al. 2023

Sci. Adv.

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Transcription factor (TF) IIIC recruits RNA polymerase (Pol) III to most of its target genes. Recognition of intragenic A- and B-box motifs in transfer RNA (tRNA) genes by TFIIIC modules τA and τB is the first critical step for tRNA synthesis but is mechanistically poorly understood. Here, we report cryo–electron microscopy structures of the six-subunit human TFIIIC complex unbound and bound to a tRNA gene. The τB module recognizes the B-box via DNA shape and sequence readout through the assembly of multiple winged-helix domains. TFIIIC220 forms an integral part of both τA and τB connecting the two subcomplexes via a ~550–amino acid residue flexible linker. Our data provide a structural mechanism by which high-affinity B-box recognition anchors TFIIIC to promoter DNA and permits scanning for low-affinity A-boxes and TFIIIB for Pol III activation.

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“…10 ), and increased expression-and protein levels of TFIIIC subunits were found in ovarian cancers 11 and during tumoral transformation 12 . Independently of its role in recruiting Pol III to its target genes, TFIIIC recognizes 'extra TFIIIC' (ETC) sites in various eukaryotes [13][14][15] and functions in genome organization by acting as a chromatin insulator 16,17 and via interaction with the architectural proteins cohesin and condensin [18][19][20][21] . TFIIIC also possesses histone acetylation activity and, together with the insulator protein CTCF, was shown to mediate long-range chromatin looping 22,23 .…”

Section: Introductionmentioning

confidence: 99%

Structural insights into human TFIIIC promoter recognition

Seifert-Davila,

Girbig,

Hauptmann

et al. 2023

Preprint

View full text Add to dashboard Cite

Transcription factor IIIC (TFIIIC) recruits RNA polymerase (Pol) III to most of its target genes. Recognition of intragenic A- and B-box motifs in tRNA genes by TFIIIC modules τA and τB is the first critical step for tRNA synthesis but is mechanistically poorly understood. Here, we report cryo-EM structures of the human 624 kDa TFIIIC complex unbound and bound to a tRNA gene. The τB module recognizes the B-box via DNA shape and sequence readout through the assembly of multiple winged-helix domains. TFIIIC220 forms an integral part of both τA and τB connecting the two subcomplexes via a ~550 amino acid residue flexible linker. Our data provide a structural mechanism by which high-affinity B-box recognition anchors TFIIIC to promoter DNA and permits scanning for low-affinity A-boxes and TFIIIB for Pol III activation.

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TFIIIC-based chromatin insulators through eukaryotic evolution

Cited by 8 publications

References 157 publications

Transcriptional reactivation of the tRNA^Ser/tRNA^Tyrgene cluster inArabidopsis thalianaroot tip (V2)

Transcriptional reactivation of the tRNA^Ser/tRNA^Tyrgene cluster inArabidopsis thalianaroot tip (V2)

Structural insights into human TFIIIC promoter recognition

Structural insights into human TFIIIC promoter recognition

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TFIIIC-based chromatin insulators through eukaryotic evolution

Cited by 8 publications

References 157 publications

Transcriptional reactivation of the tRNASer/tRNATyrgene cluster inArabidopsis thalianaroot tip (V2)

Transcriptional reactivation of the tRNASer/tRNATyrgene cluster inArabidopsis thalianaroot tip (V2)

Structural insights into human TFIIIC promoter recognition

Structural insights into human TFIIIC promoter recognition

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Product

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Transcriptional reactivation of the tRNA^Ser/tRNA^Tyrgene cluster inArabidopsis thalianaroot tip (V2)

Transcriptional reactivation of the tRNA^Ser/tRNA^Tyrgene cluster inArabidopsis thalianaroot tip (V2)