CHD chromatin remodelers and the transcription cycle

Murawska, Magdalena; Brehm, Alexander

doi:10.4161/trns.2.6.17840

Cited by 79 publications

(90 citation statements)

References 106 publications

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“…For instance, H3K9me3 has been described to be associated with silent genes (24) and to recruit HP1, which was reported as related to heterochromatin and involved in gene silencing (57). Preliminary mononucleosomal immunoprecipitation data from our laboratory, 7 indicate that, although the presence of HP1-␥ is almost negligible in nucleosome Ϫ1, in which the level of H3K9me3 is very low (Fig. 8D), HP1-␥ is clearly present in nucleosome ϩ1.…”

Section: Discussionmentioning

confidence: 86%

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Nucleosome-specific, Time-dependent Changes in Histone Modifications during Activation of the Early Growth Response 1 (Egr1) Gene

Riffo‐Campos

Castillo

Tur

et al. 2015

Journal of Biological Chemistry

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Background: Chromatin structure and histone modifications regulate transcription in eukaryotes. Results: Activation of the early growth response gene 1 involves sliding and/or eviction of nucleosomes around the transcription start site and nucleosome-specific, time-dependent changes in histone modifications. Conclusion: Remodeling mechanisms and histone modifications are specific for each nucleosome. Significance: Mononucleosomal level studies give unique information on chromatin functions.

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Section: Discussionmentioning

confidence: 86%

“…Two main remodeling mechanisms are involved in these processes, namely nucleosome sliding and partial or total histone eviction (5)(6)(7)(8)(9). For RNA polymerase processivity, nucleosomes also represent an obstacle, and they also have to be remodeled, frequently with the aid of histone chaperones (10 -13).…”

mentioning

confidence: 99%

Nucleosome-specific, Time-dependent Changes in Histone Modifications during Activation of the Early Growth Response 1 (Egr1) Gene

Riffo‐Campos

Castillo

Tur

et al. 2015

Journal of Biological Chemistry

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“…Interestingly, a variety of proteins involved in ATP-dependent chromatin remodeling (Gentry and Hennig, 2014) were isolated along with ELF7 and SPT4. So far, there is no evidence from plants, but in other organisms, CRCs are associated with the modulation of transcript elongation, probably by altering the structure of nucleosomes in transcribed regions (Murawska and Brehm, 2011;Subtil-Rodríguez and Reyes, 2011). Regarding histone modifying enzymes, only a few proteins were coisolated with the TEFs.…”

Section: Discussionmentioning

confidence: 99%

The Composition of the Arabidopsis RNA Polymerase II Transcript Elongation Complex Reveals the Interplay between Elongation and mRNA Processing Factors

et al. 2017

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Transcript elongation factors (TEFs) are a heterogeneous group of proteins that control the efficiency of transcript elongation of subsets of genes by RNA polymerase II (RNAPII) in the chromatin context. Using reciprocal tagging in combination with affinity purification and mass spectrometry, we demonstrate that in Arabidopsis thaliana, the TEFs SPT4/SPT5, SPT6, FACT, PAF1-C, and TFIIS copurified with each other and with elongating RNAPII, while P-TEFb was not among the interactors. Additionally, NAP1 histone chaperones, ATP-dependent chromatin remodeling factors, and some histone-modifying enzymes including Elongator were repeatedly found associated with TEFs. Analysis of double mutant plants defective in different combinations of TEFs revealed genetic interactions between genes encoding subunits of PAF1-C, FACT, and TFIIS, resulting in synergistic/epistatic effects on plant growth/development. Analysis of subnuclear localization, gene expression, and chromatin association did not provide evidence for an involvement of the TEFs in transcription by RNAPI (or RNAPIII). Proteomics analyses also revealed multiple interactions between the transcript elongation complex and factors involved in mRNA splicing and polyadenylation, including an association of PAF1-C with the polyadenylation factor CstF. Therefore, the RNAPII transcript elongation complex represents a platform for interactions among different TEFs, as well as for coordinating ongoing transcription with mRNA processing.

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“…29,30 According to structural features, the CHD family is divided in 3 subfamilies, with subfamily I composed of CHD2 and its closest homolog CHD1, which interacts with the trimethylated histone H3 lysine 4 (H3K4me3) mark and is associated with transcriptional activation in different organisms. [29][30][31] CHD2 carries the CHD1 residues responsible for H3K4me3 binding, and recent works have shown an almost exclusive preference of CHD2 for active promoter transcription start sites, associated with active chromatin marks. 32 In contrast, other CHD family members such as CHD3 and CHD4 have been described as expression repressors.…”

Section: Resultsmentioning

confidence: 99%

Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia

Rodrı́guez

Bretones

Quesada

et al. 2015

Blood

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Key Points• Somatic mutations alter nuclear distribution and association of CHD2 with actively transcribed genes in CLL.• CHD2 is the most frequently mutated CLL driver in the IGHV-mutated prognostic subgroup.Great progress has recently been achieved in the understanding of the genomic alterations driving chronic lymphocytic leukemia (CLL). Nevertheless, the specific molecular mechanisms governing chromatin remodeling in CLL are unknown. Here we report the genetic and functional characterization of somatic mutations affecting the chromatin remodeler CHD2, one of the most frequently mutated genes in CLL (5.3%) and in monoclonal B lymphocytosis (MBL, 7%), a B-cell expansion that can evolve to CLL. Most of the mutations affecting CHD2, identified by whole-exome sequencing of 456 CLL and 43 MBL patients, are either truncating or affect conserved residues in functional domains, thus supporting a putative role for CHD2 as a tumor suppressor gene. CHD2 mutants show altered nuclear distribution, and a chromodomain helicase DNA binding protein 2 (CHD2) mutant affected in its DNA-binding domain exhibits defective association with active chromatin. Clinicobiological analyses show that most CLL patients carrying CHD2 mutations also present mutated immunoglobulin heavy chain variable region genes (IGHVs), being the most frequently mutated gene in this prognostic subgroup. This is the first study providing functional evidence supporting CHD2 as a cancer driver and opens the way to further studies of the role of this chromatin remodeler in CLL. (Blood. 2015;126(2):195-202) IntroductionChronic lymphocytic leukemia (CLL) is the most prevalent B-cell neoplasm in Western adults. CLL shows a remarkably heterogeneous course, with some patients presenting an indolent disease and normal life span, whereas others suffer from a dismal prognosis. [1][2][3] In general, disease outcome correlates with the immunoglobulin heavy chain variable region genes (IGHV) mutational status of tumor lymphocytes, 4,5 but also with other biological features including chromosomal aberrations and the expression of CLL-specific biomarkers. [5][6][7][8] Recently, whole-genome sequencing-based reports have uncovered NOTCH1, MYD88, and XPO1 as recurrently mutated CLL drivers.9 Additionally, whole-exome sequencing approaches have identified the splicing factor SF3B1 10-13 and the shelterin complex member POT1 14 as CLL drivers associated with unfavorable prognosis. Also, mutations in sucrose isomaltase have been proposed to play a role in the CLL leukemogenic metabolic switch. 15 Moreover, clonal evolution events in CLL have been delineated, pointing to the presence of subclonal driver mutations as a relevant prognostic factor in this disease.16 Notably, mutations in many of the previously described driver genes, as well as in BRAF, EGR2, and NFKBIE, can be detected in pluripotent hematopoietic progenitor cells, indicating that founding CLL mutations appear as very early evolutionary events.17 These genomic studies have been extended by comprehensive transc...

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CHD chromatin remodelers and the transcription cycle

Cited by 79 publications

References 106 publications

Nucleosome-specific, Time-dependent Changes in Histone Modifications during Activation of the Early Growth Response 1 (Egr1) Gene

Nucleosome-specific, Time-dependent Changes in Histone Modifications during Activation of the Early Growth Response 1 (Egr1) Gene

The Composition of the Arabidopsis RNA Polymerase II Transcript Elongation Complex Reveals the Interplay between Elongation and mRNA Processing Factors

Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia

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