scholarly journals Histone sumoylation and chromatin dynamics

2021 ◽  
Author(s):  
Hong-Yeoul Ryu ◽  
Mark Hochstrasser
Keyword(s):  
Rna Polymerase Ii ◽  
Strand Break ◽  
Histone Variants ◽  
Post Translational Modifications ◽  
Chromatin Dynamics ◽  
Sumo Conjugation ◽  
Dna Double Strand Break ◽  
Transcript Elongation ◽  
Carboxy Terminal ◽  
Complex Signaling

Abstract Chromatin structure and gene expression are dynamically controlled by post-translational modifications (PTMs) on histone proteins, including ubiquitylation, methylation, acetylation and small ubiquitin-like modifier (SUMO) conjugation. It was initially thought that histone sumoylation exclusively suppressed gene transcription, but recent advances in proteomics and genomics have uncovered its diverse functions in cotranscriptional processes, including chromatin remodeling, transcript elongation, and blocking cryptic initiation. Histone sumoylation is integral to complex signaling codes that prime additional histone PTMs as well as modifications of the RNA polymerase II carboxy-terminal domain (RNAPII-CTD) during transcription. In addition, sumoylation of histone variants is critical for the DNA double-strand break (DSB) response and for chromosome segregation during mitosis. This review describes recent findings on histone sumoylation and its coordination with other histone and RNAPII-CTD modifications in the regulation of chromatin dynamics.

scholarly journals FCP1, a Phosphatase Specific for the Heptapeptide Repeat of the Largest Subunit of RNA Polymerase II, Stimulates Transcription Elongation

2002 ◽  
Vol 22 (21) ◽  
pp. 7543-7552 ◽  
Author(s):  
Subhrangsu S. Mandal ◽  
Helen Cho ◽  
Sungjoon Kim ◽  
Kettly Cabane ◽  
Danny Reinberg
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcription Elongation ◽  
Carboxy Terminal Domain ◽  
Transcription Factor Iif ◽  
Transcript Elongation ◽  
Rnap Ii ◽  
Carboxy Terminal

ABSTRACT FCP1, a phosphatase specific for the carboxy-terminal domain of RNA polymerase II (RNAP II), was found to stimulate transcript elongation by RNAP II in vitro and in vivo. This activity is independent of and distinct from the elongation-stimulatory activity associated with transcription factor IIF (TFIIF), and the elongation effects of TFIIF and FCP1 were found to be additive. Genetic experiments resulted in the isolation of several distinct fcp1 alleles. One of these alleles was found to suppress the slow-growth phenotype associated with either the reduction of intracellular nucleotide concentrations or the inhibition of other transcription elongation factors. Importantly, this allele of fcp1 was found to be lethal when combined individually with two mutations in the second-largest subunit of RNAP II, which had been shown previously to affect transcription elongation.

Proteome analysis of protein partners to nucleosomes containing canonical H2A or the variant histones H2A.Z or H2A.X

2012 ◽  
Vol 393 (1-2) ◽  
pp. 47-61 ◽  
Author(s):  
Satoru Fujimoto ◽  
Corrine Seebart ◽  
Tiziana Guastafierro ◽  
Jessica Prenni ◽  
Paola Caiafa ◽  
...  
Keyword(s):  
Regulation Of Gene Expression ◽  
Proteome Analysis ◽  
Strand Break ◽  
Histone Variants ◽  
Histone H2a ◽  
Systematic Analysis ◽  
Cellular Processes ◽  
Nucleosome Structure ◽  
Protein Partners ◽  
Dna Double Strand Break

Abstract Although the existence of histone variants has been known for quite some time, only recently are we grasping the breadth and diversity of the cellular processes in which they are involved. Of particular interest are the two variants of histone H2A, H2A.Z and H2A.X because of their roles in regulation of gene expression and in DNA double-strand break repair, respectively. We hypothesize that nucleosomes containing these variants may perform their distinct functions by interacting with different sets of proteins. Here, we present our proteome analysis aimed at identifying protein partners that interact with nucleosomes containing H2A.Z, H2A.X or their canonical H2A counterpart. Our development of a nucleosome-pull down assay and analysis of the recovered nucleosome-interacting proteins by mass spectrometry allowed us to directly compare nuclear partners of these variant-containing nucleosomes to those containing canonical H2A. To our knowledge, our data represent the first systematic analysis of the H2A.Z and H2A.X interactome in the context of nucleosome structure.

scholarly journals Beyond reversal: ubiquitin and ubiquitin-like proteases and the orchestration of the DNA double strand break repair response

2019 ◽  
Vol 47 (6) ◽  
pp. 1881-1893
Author(s):  
Alexander J. Garvin
Keyword(s):  
Protein Interactions ◽  
Cellular Response ◽  
Strand Break ◽  
Central Component ◽  
Protein Protein Interactions ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Post Translational Modifications ◽  
Strand Breaks ◽  
Dna Double Strand Break

The cellular response to genotoxic DNA double strand breaks (DSBs) uses a multitude of post-translational modifications to localise, modulate and ultimately clear DNA repair factors in a timely and accurate manner. Ubiquitination is well established as vital to the DSB response, with a carefully co-ordinated pathway of histone ubiquitination events being a central component of DSB signalling. Other ubiquitin-like modifiers (Ubl) including SUMO and NEDD8 have since been identified as playing important roles in DSB repair. In the last five years ∼20 additional Ub/Ubl proteases have been implicated in the DSB response. The number of proteases identified highlights the complexity of the Ub/Ubl signal present at DSBs. Ub/Ubl proteases regulate turnover, activity and protein–protein interactions of DSB repair factors both catalytically and non-catalytically. This not only ensures efficient repair of breaks but has a role in channelling repair into the correct DSB repair sub-pathways. Ultimately Ub/Ubl proteases have essential roles in maintaining genomic stability. Given that deficiencies in many Ub/Ubl proteases promotes sensitivity to DNA damaging chemotherapies, they could be attractive targets for cancer treatment.

scholarly journals The Chd1 chromatin remodeler shifts hexasomes unidirectionally

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Robert F Levendosky ◽  
Anton Sabantsev ◽  
Sebastian Deindl ◽  
Gregory D Bowman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Histone Variants ◽  
Chromatin Remodeler ◽  
Post Translational Modifications ◽  
Pol Ii ◽  
Specific Orientation ◽  
Chromatin Reorganization

Despite their canonical two-fold symmetry, nucleosomes in biological contexts are often asymmetric: functionalized with post-translational modifications (PTMs), substituted with histone variants, and even lacking H2A/H2B dimers. Here we show that the Widom 601 nucleosome positioning sequence can produce hexasomes in a specific orientation on DNA, providing a useful tool for interrogating chromatin enzymes and allowing for the generation of nucleosomes with precisely defined asymmetry. Using this methodology, we demonstrate that the Chd1 chromatin remodeler from Saccharomyces cerevisiae requires H2A/H2B on the entry side for sliding, and thus, unlike the back-and-forth sliding observed for nucleosomes, Chd1 shifts hexasomes unidirectionally. Chd1 takes part in chromatin reorganization surrounding transcribing RNA polymerase II (Pol II), and using asymmetric nucleosomes we show that ubiquitin-conjugated H2B on the entry side stimulates nucleosome sliding by Chd1. We speculate that biased nucleosome and hexasome sliding due to asymmetry contributes to the packing of arrays observed in vivo.

Release of paused RNA polymerase II at specific loci favors DNA double-strand-break formation and promotes cancer translocations

2019 ◽  
Vol 51 (6) ◽  
pp. 1011-1023 ◽  
Author(s):  
Gaetano Ivan Dellino ◽  
Fernando Palluzzi ◽  
Andrea Maria Chiariello ◽  
Rossana Piccioni ◽  
Simona Bianco ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Strand Break ◽  
Double Strand Break ◽  
Dna Double Strand Break ◽  
Break Formation

Epigenetic chromatin changes and the transcription cycle

2019 ◽  
pp. 57-68
Author(s):  
John C. Lucchesi
Keyword(s):  
Rna Polymerase Ii ◽  
Histone Modifications ◽  
Histone Variants ◽  
Gene Promoters ◽  
Chromatin Remodelers ◽  
Dna Binding Sites ◽  
Core Histones ◽  
Transcript Elongation ◽  
Pioneer Factors ◽  
Histone Octamers

In order to allow transcription to occur, the association of DNA with histone octamers and the compacted physical state of the chromatin fiber must be modified by the opportunistic binding of pioneer transcription factors to their cognate DNA binding sites. Once bound, pioneer factors recruit chromatin remodelers and histone-modifying enzymes for the purpose of repositioning nucleosomes and exposing regulatory regions (enhancers and gene promoters) to the components necessary for the initiation of transcription. Histone modifications, such as acetylation, methylation and ubiquitination, and the dynamic phosphorylation of specific amino acids on the major RNA polymerase II subunit activate transcription and attract the factors necessary to eliminate the pausing that normally occurs soon after initiation. Further histone modifications and the replacement of certain core histones by histone variants facilitate transcript elongation and termination. Two additional major epigenetic modifications that impact the process of transcription consist of the action of non-coding RNAs and DNA methylation.

scholarly journals The Role of Polycomb Group Protein BMI1 in DNA Repair and Genomic Stability

2021 ◽  
Vol 22 (6) ◽  
pp. 2976
Author(s):  
Amira Fitieh ◽  
Andrew J. Locke ◽  
Mobina Motamedi ◽  
Ismail Hassan Ismail
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Gene Silencing ◽  
Strand Break ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Post Translational Modifications ◽  
Dna Damage Signaling ◽  
Dna Double Strand Break ◽  
Group Protein

The polycomb group (PcG) proteins are a class of transcriptional repressors that mediate gene silencing through histone post-translational modifications. They are involved in the maintenance of stem cell self-renewal and proliferation, processes that are often dysregulated in cancer. Apart from their canonical functions in epigenetic gene silencing, several studies have uncovered a function for PcG proteins in DNA damage signaling and repair. In particular, members of the poly-comb group complexes (PRC) 1 and 2 have been shown to recruit to sites of DNA damage and mediate DNA double-strand break repair. Here, we review current understanding of the PRCs and their roles in cancer development. We then focus on the PRC1 member BMI1, discussing the current state of knowledge of its role in DNA repair and genome integrity, and outline how it can be targeted pharmacologically.

scholarly journals Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Nicolas Descostes ◽  
Martin Heidemann ◽  
Lionel Spinelli ◽  
Roland Schüller ◽  
Muhammad Ahmad Maqbool ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Mammalian Cells ◽  
Consensus Sequence ◽  
Post Translational Modifications ◽  
Pol Ii ◽  
Carboxy Terminal Domain ◽  
Mrna Maturation ◽  
Carboxy Terminal ◽  
Rna Polymerase Ii Ctd

In mammals, the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II consists of 52 conserved heptapeptide repeats containing the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Post-translational modifications of the CTD coordinate the transcription cycle and various steps of mRNA maturation. Here we describe Tyr1 phosphorylation (Tyr1P) as a hallmark of promoter (5′ associated) Pol II in mammalian cells, in contrast to what was described in yeast. Tyr1P is predominantly found in antisense orientation at promoters but is also specifically enriched at active enhancers. Mutation of Tyr1 to phenylalanine (Y1F) prevents the formation of the hyper-phosphorylated Pol IIO form, induces degradation of Pol II to the truncated Pol IIB form, and results in a lethal phenotype. Our results suggest that Tyr1P has evolved specialized and essential functions in higher eukaryotes associated with antisense promoter and enhancer transcription, and Pol II stability.

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