Publications by authors named "Guillaume Charbonnier"

19 Publications

  • Page 1 of 1

PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL.

Blood 2021 Jun 14. Epub 2021 Jun 14.

Institut Necker Enfants-Malades, Team 2, INSERM U1151, Paris, France.

T-cell acute lymphoblastic leukemia (T-ALL) are aggressive hematological cancers with dismal outcomes, and are in need of new therapeutic options. Polycomb Repressor Complex 2 (PRC2) loss-of-function alterations were reported in pediatric T-ALL; yet their clinical relevance and functional consequences remain elusive. Here, we extensively analyzed PRC2 alterations in a large series of 218 adult T-ALL patients. We found that PRC2 genetic lesions are frequent events in T-ALL and are not restricted to ETP-ALL. PRC2 loss of function associates with activating mutations of the IL7R/JAK/STAT pathway. PRC2-altered T-ALL patients poorly respond to prednisone, have low bone marrow blast clearance, and persistent minimal residual disease. Furthermore, we identified that PRC2 loss of function profoundly reshapes the genetic and epigenetic landscapes, leading to the reactivation of stem cell programs that cooperate with Bromodomain and Extraterminal (BET) proteins to sustain T-ALL. This study identifies BET proteins as key mediators of the PRC2 loss of function-induced remodeling. Our data has uncovered a targetable vulnerability to BET inhibition that can be exploited to treat PRC2-altered T-ALL patients.
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http://dx.doi.org/10.1182/blood.2020010081DOI Listing
June 2021

Timing and Spectrum of Neurological Complications After Flow Diverter Implantation for Intracranial Aneurysms.

Front Neurol 2021 20;12:590383. Epub 2021 Apr 20.

Interventional Neuroradiology, Rothschild Foundation Hospital, Paris, France.

The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications. This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD. Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186-1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month. Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.
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http://dx.doi.org/10.3389/fneur.2021.590383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093792PMC
April 2021

Intracranial Bleeding After Reperfusion Therapy in Acute Ischemic Stroke.

Front Neurol 2020 9;11:629920. Epub 2021 Feb 9.

Neurology Department, Besançon University Hospital, Besançon, France.

Intracranial hemorrhage is one of the most feared complications following brain infarct. Ischemic tissues have a natural tendency to bleed. Moreover, the first recanalization trials using intravenous thrombolysis have shown an increase in mild to severe intracranial hemorrhage. Symptomatic intracerebral hemorrhage is strongly associated with poor outcomes and is an important factor in recanalization decisions. Stroke physicians have to weigh the potential benefit of recanalization therapies, first, with different risks of intracranial hemorrhage described in randomized controlled trials, and second with numerous risk markers that have been found to be associated with intracranial hemorrhage in retrospective series. These decisions have become quite complex with different intravenous thrombolytics and mechanical thrombectomy. This review aims to outline some elements of the pathophysiological mechanisms and classifications, describe most of the risk factors identified for each reperfusion therapy, and finally suggest future research directions that could help physicians dealing with these complications.
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http://dx.doi.org/10.3389/fneur.2020.629920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900408PMC
February 2021

[Interest of telemedicine for hospitals with no stroke unit].

Rev Prat 2020 06;70(6):632-634

Unité de soins intensifs neurovasculaires, département de neurologie, CHU de Besançon, Besançon, France.

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June 2020

Alternative Enhancer Usage and Targeted Polycomb Marking Hallmark Promoter Choice during T Cell Differentiation.

Cell Rep 2020 08;32(7):108048

Institut de Génétique Moléculaire de Montpellier, Université de Montpellier, CNRS, 1919 Route de Mende, Montpellier 34293, France. Electronic address:

During thymic development and upon peripheral activation, T cells undergo extensive phenotypic and functional changes coordinated by lineage-specific developmental programs. To characterize the regulatory landscape controlling T cell identity, we perform a wide epigenomic and transcriptional analysis of mouse thymocytes and naive CD4 differentiated T helper cells. Our investigations reveal a dynamic putative enhancer landscape, and we could validate many of the enhancers using the high-throughput CapStarr sequencing (CapStarr-seq) approach. We find that genes using multiple promoters display increased enhancer usage, suggesting that apparent "enhancer redundancy" might relate to isoform selection. Furthermore, we can show that two Runx3 promoters display long-range interactions with specific enhancers. Finally, our analyses suggest a novel function for the PRC2 complex in the control of alternative promoter usage. Altogether, our study has allowed for the mapping of an exhaustive set of active enhancers and provides new insights into their function and that of PRC2 in controlling promoter choice during T cell differentiation.
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http://dx.doi.org/10.1016/j.celrep.2020.108048DOI Listing
August 2020

Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation.

J Exp Med 2020 09;217(9)

Université de Paris (Descartes), Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France.

Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status. Among these, the TCRA gene enhancer (Eα) is in an open and unmethylated chromatin structure well before activation. Integrative analyses revealed that the HOXA5-9 transcription factors repress the Eα enhancer at early stages of T cell differentiation, while their decommission is required for TCRA locus activation and enforced αβ T lineage differentiation. Remarkably, the HOXA-mediated repression of Eα is paralleled by the ectopic expression of homeodomain-related oncogenes in T cell acute lymphoblastic leukemia. These results highlight an analogous enhancer repression mechanism at play in normal and cancer conditions, but imposing distinct developmental constraints.
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http://dx.doi.org/10.1084/jem.20192360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478722PMC
September 2020

Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene.

PLoS One 2020 26;15(5):e0233191. Epub 2020 May 26.

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.

The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-throughput enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250416PMC
August 2020

Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak: Decreased Activity, and Increased Care Delays.

Stroke 2020 07 20;51(7):2012-2017. Epub 2020 May 20.

Neuroradiology Department, CH Sainte-Anne, Paris, France (B.K., W.B.H., G.B.).

Background And Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT).

Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value).

Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76-0.82]; <0.001) in MT case volumes during the epidemic period, and a significant increase in delays between imaging and groin puncture, overall (mean 144.9±SD 86.8 minutes versus 126.2±70.9; <0.001 in 2019) and in transferred patients (mean 182.6±SD 82.0 minutes versus 153.25±67; <0.001). After the instatement of strict epidemic mitigation measures, there was a significant negative correlation between the number of hospitalizations for COVID and the number of MT cases ( -0.51; =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both <0.05).

Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution.
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http://dx.doi.org/10.1161/STROKEAHA.120.030373DOI Listing
July 2020

Does Intravenous Thrombolysis Influence the Time of Recanalization and Success of Mechanical Thrombectomy during the Acute Phase of Cerebral Infarction?

Cerebrovasc Dis Extra 2020 28;10(1):28-35. Epub 2020 Apr 28.

Interventional Neuroradiology department, Besançon University Hospital, Besançon, France.

Objectives: Mechanical thrombectomy (MT) is an effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusion. Recanalization time is a key factor in the treatment of AIS. It has previously been suggested that intravenous thrombolysis (IVT) may be associated with a shorter recanalization time. The aim of our study was to investigate whether IVT or other factors could be associated with shorter or longer MT procedure times.

Methods: We performed a retrospective analysis of a local cohort of patients treated by MT. We collected procedure time (puncture to recanalization and clot visualization to recanalization), demographic data, localization of the thrombus, antithrombotic treatment at arrival, IVT infusion, and stroke subtype at discharge according to the TOAST classification. We planned to analyze the full cohort and the successful revascularization subgroup.

Results: There was no difference in procedure times between patients who received IVT and those who did not. In the successful revascularization subgroup, patients presenting with cardioembolic stroke had a significantly shorter time between clot visualizations and revascularization than the other patients (41 vs. 56 min, p = 0.024), but this was not the case in the full cohort. Also in the successful revascularization subgroup, the revascularization time was 76 vs. 61 min (p = 0.075) in patients presenting with tandem occlusion vs. the others, but there was no difference between these groups in the full cohort.

Conclusions: There was no difference in terms of procedure times in patients treated by IVT and MT vs. patients treated by MT alone either in the full cohort or in the successful revascularization subgroup. The data from the successful revascularization subgroup may be useful for studying revascularization times, provided that data from procedures that were stopped prematurely by the operator due to the length of time since symptom onset is removed.
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http://dx.doi.org/10.1159/000507119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289153PMC
June 2020

RNA-Guided Genomic Localization of H2A.L.2 Histone Variant.

Cells 2020 02 18;9(2). Epub 2020 Feb 18.

CNRS UMR 5309, Inserm, U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, F-38700 Grenoble, France.

The molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B-H2A.L.2 allows a controlled replacement of histones by protamines to occur. Here, we highlight the intrinsic ability of H2A.L.2 to specifically target the pericentric regions of the genome and discuss why pericentric heterochromatin is a privileged site of histone retention in mature spermatozoa. We observed that the intranuclear localization of H2A.L.2 is controlled by its ability to bind RNA, as well as by an interplay between its RNA-binding activity and its tropism for pericentric heterochromatin. We identify the H2A.L.2 RNA-binding domain and demonstrate that in somatic cells, the replacement of H2A.L.2 RNA-binding motif enhances and stabilizes its pericentric localization, while the forced expression of RNA increases its homogenous nuclear distribution. Based on these data, we propose that the specific accumulation of RNA on pericentric regions combined with H2A.L.2 tropism for these regions are responsible for stabilizing H2A.L.2 on these regions in mature spermatozoa. This situation would favor histone retention on pericentric heterochromatin.
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http://dx.doi.org/10.3390/cells9020474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072763PMC
February 2020

[Stroke prevention].

Presse Med 2019 Jun 29;48(6):655-663. Epub 2019 May 29.

Hôpital Bretonneau, université François-Rabelais de Tours, centre hospitalier régional universitaire de Tours, service de neuroradiologie interventionnelle, 37000 Tours, France.

Prevention is essential to stroke management because of the high risk of recurrence. Stroke incidence is increased by known risk factors, which can be prevented. Cardiovascular prevention after stroke or TIA also includes aetiology-specific treatment, when it is known. Endovascular treatment is not indicated as a first-line treatment for atheromatous cervical or intracranial stenosis. Endovascular or surgical treatment is not indicated as first-line treatment for cervical arterial dissection because of its minor risk of stroke recurrence.
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http://dx.doi.org/10.1016/j.lpm.2019.05.001DOI Listing
June 2019

Quantitative evaluation of WEB shape modification: A five-year follow-up study.

J Neuroradiol 2020 May 7;47(3):193-196. Epub 2019 Mar 7.

University Hospital of Reims, Neuroradiology Department, 45, rue Cognacq-Jay, 51100 Reims, France.

Background And Purpose: Web shape modification (WSM) has previously been associated with aneurysm recurrence. We report here our five-year experience of WEB device use with a quantitative approach of the WSM phenomenon.

Methods: From July 2012 to July 2017, 50 patients with 51 unruptured aneurysms treated with the WEB device have been prospectively enrolled in our data base and retrospectively analyzed. An independent "core lab" evaluated anatomical results and potential WSM in DSA follow-up. We defined the WSM ratio (WSMr) as a relative index between the height and the width of the device in working projections which gave an evaluation of the device deformation over the time.

Results: During the total follow-up period, WSM was observed in 35/48 aneurysms (72.9%). Adequate occlusion rates were 87.0% and 92.6% with and without WSM respectively (P = 0.65). 30 out the 35 (85.7%) shape modifications were already noticed at short-term follow-up (6-month DSA). 33 patients had 2 DSA controls and WSMr measurements were available in 24 patients: 18 (75%) with WSM and 6 (25%) without WSM. In the group with WSM, WSMr values were 0.80 in post-embolization, 0.52 at the first DSA angiogram and 0.42 at the second DSA angiogram.

Conclusion: WEB shape modification was observed in more than half of cases but with no influence regarding adequate occlusion rate. This quantitative approach of WSM highlights that this phenomenon appears to be early and progressive over time. This supports the hypothesis that WSM could be more probably related to aneurysm healing rather than external compression.
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http://dx.doi.org/10.1016/j.neurad.2019.02.010DOI Listing
May 2020

Visual assessment of diffusion weighted imaging infarct volume lacks accuracy and reliability.

J Neurointerv Surg 2019 Sep 2;11(9):947-954. Epub 2019 Feb 2.

Unit of Clinical Research, Fondation Rothschild Hospital, Paris, France.

Purpose: The DAWN trial (Diffusion weighted imaging or CT perfusion Assessment with clinical mismatch in the triage of Wake-up and late presenting strokes undergoing Neurointervention with Trevo) has demonstrated the benefits of thrombectomy in patients with unknown or late onset strokes, using automated software (RAPID) for measurement of infarct volume. Because RAPID is not available in all centers, we aimed to assess the accuracy and repeatability of visual infarct volume estimation by clinicians and the consequences for thrombectomy decisions based on the DAWN criteria.

Materials And Methods: 18 physicians, who routinely depend on MRI for acute stroke imaging, assessed 32 MR scans selected from a prospective databaseover two independent sessions. Raters were asked to visually estimate the diffusion weighted imaging (DWI) infarct volume for each case. Sensitivity, specificity, and accuracy of the estimated volumes were compared with the available RAPID measurements for various volume cut-off points. Thrombectomy decisions based on DAWN criteria with RAPID measurements and raters' visual estimates were compared. Inter-rater and intra-rater agreement was measured using kappa statistics.

Results: The mean accuracy of raters was <90% for all volume cut-points. Inter-rater agreement was below substantial for each DWI infarct volume cut-off points. Intra-rater agreement was substantial for 55-83% of raters, depending on the selected cut-off points. Applying DAWN criteria with visual estimates instead of RAPID measurements led to 19% erroneous thrombectomy decisions, and showed a lack of reproducibility.

Conclusion: The visual assessment of DWI infarct volume lacks accuracy and repeatability, and could lead to a significant number of erroneous decisions when applying the DAWN criteria.
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http://dx.doi.org/10.1136/neurintsurg-2018-014613DOI Listing
September 2019

[Neuro-lupus revealed by a hemiparesis and abnormal movements of a teenager].

Presse Med 2019 Feb 18;48(2):195-198. Epub 2019 Jan 18.

CHRU de Besançon, département de neurologie, 3, boulevard Alexandre-Fleming, 25000 Besançon, France.

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http://dx.doi.org/10.1016/j.lpm.2018.11.021DOI Listing
February 2019

Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells.

Cell Rep 2018 09;24(13):3477-3487.e6

CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France. Electronic address:

Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome.
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http://dx.doi.org/10.1016/j.celrep.2018.08.069DOI Listing
September 2018

Genome-wide characterization of mammalian promoters with distal enhancer functions.

Nat Genet 2017 Jul 5;49(7):1073-1081. Epub 2017 Jun 5.

Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France.

Gene expression in mammals is precisely regulated by the combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might have enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease.
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http://dx.doi.org/10.1038/ng.3884DOI Listing
July 2017

Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells.

Mol Cell 2017 Apr 30;66(1):89-101.e8. Epub 2017 Mar 30.

CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France. Electronic address:

Histone replacement by transition proteins (TPs) and protamines (Prms) constitutes an essential step for the successful production of functional male gametes, yet nothing is known on the underlying functional interplay between histones, TPs, and Prms. Here, by studying spermatogenesis in the absence of a spermatid-specific histone variant, H2A.L.2, we discover a fundamental mechanism involved in the transformation of nucleosomes into nucleoprotamines. H2A.L.2 is synthesized at the same time as TPs and enables their loading onto the nucleosomes. TPs do not displace histones but rather drive the recruitment and processing of Prms, which are themselves responsible for histone eviction. Altogether, the incorporation of H2A.L.2 initiates and orchestrates a series of successive transitional states that ultimately shift to the fully compacted genome of the mature spermatozoa. Hence, the current view of histone-to-nucleoprotamine transition should be revisited and include an additional step with H2A.L.2 assembly prior to the action of TPs and Prms.
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http://dx.doi.org/10.1016/j.molcel.2017.02.025DOI Listing
April 2017

Mercury enrichment indicates volcanic triggering of Valanginian environmental change.

Sci Rep 2017 01 20;7:40808. Epub 2017 Jan 20.

Institute of Earth Sciences, Géopolis, University of Lausanne, CH-1015 Lausanne, Switzerland.

The Valanginian stage (Early Cretaceous) includes an episode of significant environmental changes, which are well defined by a positive δC excursion. This globally recorded excursion indicates important perturbations in the carbon cycle, which has tentatively been associated with a pulse in volcanic activity and the formation of the Paraná-Etendeka large igneous province (LIP). Uncertainties in existing age models preclude, however, its positive identification as a trigger of Valanginian environmental changes. Here we report that in Valanginian sediments recovered from a drill core in Wąwał (Polish Basin, Poland), and from outcrops in the Breggia Gorge (Lombardian Basin, southern Switzerland), and Orpierre and Angles (Vocontian Basin, SE France), intervals at or near the onset of the positive δC excursion are significantly enriched in mercury (Hg). The persistence of the Hg anomaly in Hg/TOC, Hg/phyllosilicate, and Hg/Fe ratios shows that organic-matter scavenging and/or adsorbtion onto clay minerals or hydrous iron oxides only played a limited role. Volcanic outgassing was most probably the primary source of the Hg enrichments, which demonstrate that an important magmatic pulse triggered the Valanginian environmental perturbations.
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http://dx.doi.org/10.1038/srep40808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247756PMC
January 2017

Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters.

Mol Cell 2016 04;62(2):169-180

CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France. Electronic address:

Recently discovered histone lysine acylation marks increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters where acetylation guides the binding of Brdt, a bromodomain-containing protein, thereby mediating stage-specific gene expression programs and post-meiotic chromatin reorganization. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbor competing histone acetylation and butyrylation marks at H4 K5 and H4 K8. Despite acting as a direct stimulator of transcription, histone butyrylation competes with acetylation, especially at H4 K5, to prevent Brdt binding. Additionally, H4 K5K8 butyrylation also marks retarded histone removal during late spermatogenesis. Hence, alternating H4 acetylation and butyrylation, while sustaining direct gene activation and dynamic bromodomain binding, could impact the final male epigenome features.
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http://dx.doi.org/10.1016/j.molcel.2016.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850424PMC
April 2016