Eukaryotic Multi-Subunit RNA Polymerases, General Transcription Factors, and the CTD

In eukaryotes, transcription of protein-coding genes requires the assembly at core promoters of a large preinitiation machinery containing RNA polymerase II (RNAPII) and general transcription factors (GTFs). Transcription is potentiated by regulatory elements called enhancers, which are recognized by specific DNA-binding transcription factors that recruit cofactors and convey, following chromatin remodeling, the activating cues to the preinitiation complex. This review summarizes nearly five decades of work on transcription initiation by describing the sequential recruitment of diverse molecular players including the GTFs, the Mediator complex, and DNA repair factors that support RNAPII to enable RNA synthesis. The elucidation of the transcription initiation mechanism has greatly benefited from the study of altered transcription components associated with human diseases that could be considered transcription syndromes.

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DOT1L Complex Regulates Transcriptional Initiation 1 in Human Cells

10.1101/2020.12.07.414722 ◽

2020 ◽

Author(s):

Ming Yu ◽

Robert Roeder ◽

Aiwei Wu ◽

Junhong Zhi ◽

Tian Tian ◽

...

Keyword(s):

Transcription Factors ◽

Elongation Factor ◽

Elongation Rate ◽

Human Cells ◽

Mixed Lineage Leukemia ◽

Transcriptional Elongation ◽

Saga Complex ◽

Transcriptional Initiation ◽

Pol Ii ◽

General Transcription Factors

DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17 and ENL/AF9, is dysregulated in most of the cases of mixed lineage leukemia (MLL) and is believed to regulate transcriptional elongation without much evidence. Here we show that DOT1L depletion reduced the global occupancy without affecting the traveling ratio or the elongation rate of Pol II, suggesting it not a major elongation factor. An examination of general transcription factors binding revealed globally reduced TBP and TFIIA occupancies near promoters after DOT1L loss, pointing to a role in transcriptional initiation. Proteomic studies uncovered that DOT1L regulates transcriptional initiation likely by facilitating the recruitment of TFIID. Moreover, ENL, a DOT1L complex subunit with a known role in DOT1L recruitment, also regulates transcriptional initiation. Furthermore, DOT1L stimulates H2B monoubiquitination by limiting the recruitment of human SAGA complex, and the connection between Dot1/DOT1L and SAGA complex is conserved between yeast and human. These results advanced current understanding of roles of DOT1L complex in transcriptional regulation and MLL.

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The essential activities of the bacterial sigma factor

Canadian Journal of Microbiology ◽

10.1139/cjm-2016-0576 ◽

2017 ◽

Vol 63 (2) ◽

pp. 89-99 ◽

Cited By ~ 16

Author(s):

Maria C. Davis ◽

Christopher A. Kesthely ◽

Emily A. Franklin ◽

Shawn R. MacLellan

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Rna Synthesis ◽

Gene Expression Regulation ◽

Structure And Function ◽

Structural Studies ◽

General Transcription Factors ◽

Transcription Process ◽

Promoter Dna ◽

And Function

Transcription is the first and most heavily regulated step in gene expression. Sigma (σ) factors are general transcription factors that reversibly bind RNA polymerase (RNAP) and mediate transcription of all genes in bacteria. σ Factors play 3 major roles in the RNA synthesis initiation process: they (i) target RNAP holoenzyme to specific promoters, (ii) melt a region of double-stranded promoter DNA and stabilize it as a single-stranded open complex, and (iii) interact with other DNA-binding transcription factors to contribute complexity to gene expression regulation schemes. Recent structural studies have demonstrated that when σ factors bind promoter DNA, they capture 1 or more nucleotides that are flipped out of the helical DNA stack and this stabilizes the promoter open-complex intermediate that is required for the initiation of RNA synthesis. This review describes the structure and function of the σ70 family of σ proteins and the essential roles they play in the transcription process.

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A chromomeric model for nuclear and chromosome structure

Journal of Cell Science ◽

10.1242/jcs.108.9.2927 ◽

1995 ◽

Vol 108 (9) ◽

pp. 2927-2935 ◽

Cited By ~ 7

Author(s):

P.R. Cook

Keyword(s):

Transcription Factors ◽

Chromosome Structure ◽

Rna Polymerases ◽

Stable Structure ◽

Structural Elements ◽

Transcription Factories ◽

Chromatin Loops ◽

Sticky End

The basic structural elements of chromatin and chromosomes are reviewed. Then a model involving only three architectural motifs, nucleosomes, chromatin loops and transcription factories/chromomeres, is presented. Loops are tied through transcription factors and RNA polymerases to factories during interphase and to the remnants of those factories, chromomeres, during mitosis. On entry into mitosis, increased adhesiveness between nucleosomes and between factories drives a ‘sticky-end’ aggregation to the most compact and stable structure, a cylinder of nucleosomes around an axial chromomeric core.

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General Transcription Factors

Encyclopedia of Molecular Pharmacology ◽

10.1007/978-3-540-38918-7_5772 ◽

2008 ◽

pp. 535-535

Keyword(s):

Transcription Factors ◽

General Transcription Factors

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Interaction of the TFIIB zinc ribbon with RNA polymerase II

Biochemical Society Transactions ◽

10.1042/bst0360595 ◽

2008 ◽

Vol 36 (4) ◽

pp. 595-598 ◽

Cited By ~ 6

Author(s):

Laura M. Elsby ◽

Stefan G.E. Roberts

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Structural Models ◽

Initiation Complex ◽

General Transcription Factors ◽

Transcription Factor Iib ◽

General Transcription Factor ◽

Zinc Ribbon

Transcription by RNA polymerase II requires the assembly of the general transcription factors at the promoter to form a pre-initiation complex. The general transcription factor TF (transcription factor) IIB plays a central role in the assembly of the pre-initiation complex, providing a bridge between promoter-bound TFIID and RNA polymerase II/TFIIF. We have characterized a series of TFIIB mutants in their ability to support transcription and recruit RNA polymerase II to the promoter. Our analyses identify several residues within the TFIIB zinc ribbon that are required for RNA polymerase II assembly. Using the structural models of TFIIB, we describe the interface between the TFIIB zinc ribbon region and RNA polymerase II.

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