Deregulated expression of <i>EZH2</i> in congenital brainstem disconnection

Barth, P. G.; Aronica, Eleonora; Fox, Stéphanie; Fluiter, Kees; Weterman, Marian A. J.; Poretti, Andrea; Miller, Douglas C.; Boltshauser, Eugen; Harding, Brian; Santi, Mariarita; Baas, Frank

doi:10.1111/nan.12368

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…anti-H3K4me2 rabbit polyclonal 1/500 Millipore (07-030) [13][14][15] anti-H3K4me3 rabbit polyclonal 1/500 Abcam (ab8580) [16][17][18] anti-H3K9me3 rabbit polyclonal 1/500 Abcam (ab8898) [19][20][21] anti-H3K27ac rabbit polyclonal 1/500 Abcam (ab4729) [22][23][24] anti-H3K27me2 rabbit polyclonal 1/500 Abcam (ab24684) [25,26] anti-H3K27me3 rabbit polyclonal 1/500 Millipore (07-449) [24,[27][28][29] anti-H3K79me2 rabbit polyclonal 1/500 Abcam (ab3594) [30][31][32] anti-H3K79me3 rabbit polyclonal 1/500 Abcam (ab2621) [33][34][35] anti-SCP3 mouse monoclonal 1/500 Abcam (ab97672) [36][37][38] anti-α-Tubulin (S2 Fig) mouse monoclonal 1/500 Sigma-Aldrich (T6199) [39,40] All antibodies are commercially available, and their specificity has been reported in previous studies.…”

Section: Antibody Name Source Dilution Company (Catalogue) Referencementioning

confidence: 99%

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

et al. 2020

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Human epidemiological studies have shown that paternal aging as one of the risk factors for neurodevelopmental disorders, such as autism, in offspring. A recent study has suggested that factors other than de novo mutations due to aging can influence the biology of offspring. Here, we focused on epigenetic alterations in sperm that can influence developmental programs in offspring. In this study, we qualitatively and semiquantitatively evaluated histone modification patterns in male germline cells throughout spermatogenesis based on immunostaining of testes taken from young (3 months old) and aged (12 months old) mice. Although localization patterns were not obviously changed between young and aged testes, some histone modification showed differences in their intensity. Among histone modifications that repress gene expression, histone H3 lysine 9 trimethylation (H3K9me3) was decreased in the male germline cells of the aged testis, while H3K27me2/3 was increased. The intensity of H3K27 acetylation (ac), an active mark, was lower/higher depending on the stages in the aged testis. Interestingly, H3K27ac was detected on the putative sex chromosomes of round spermatids, while other chromosomes were occupied by a repressive mark, H3K27me3. Among other histone modifications that activate gene expression, H3K4me2 was drastically decreased in the male germline cells of the aged testis. In contrast, H3K79me3 was increased in M-phase spermatocytes, where it accumulates on the sex chromosomes. Therefore, aging induced alterations in the amount of histone modifications and in the differences of patterns for each modification. Moreover, histone modifications on the sex chromosomes and on other chromosomes seems to be differentially regulated by aging. These findings will help elucidate the epigenetic mechanisms underlying the influence of paternal aging on offspring development.

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Section: Antibody Name Source Dilution Company (Catalogue) Referencementioning

confidence: 99%

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

et al. 2020

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“…In addition, the overall neuroimaging pattern observed in our patients is very different from those reported in defined brainstem malformations, in particular pontine tegmental cap dysplasia, 15,16 horizontal gaze palsy, and progressive scoliosis due to pathogenic variants in the ROBO3 gene, 17 diencephalic-mesencephalic junction dysplasia, 18 tubulinopathies with brainstem involvement, 19 and brainstem disconnection. 20,21 It is not possible to exactly date the destructive event, but we think that there is compelling support for a prenatal injury: patients 1, 3, and 4 were symptomatic immediately after birth, polyhydramnios in patients 3 and 4 is most likely caused by prenatal swallowing impairment secondary to dysfunction of the fetal brainstem, and neuroimaging studies showed abnormal findings on day 1 (patient 4), day 9 (patient 1), and day 20 (patient 3) of life.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Brainstem Disruptions: Small Lesions–Big Problems

et al. 2017

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Prenatal disruptive injuries within one or both cerebellar hemispheres, which are mostly caused by hemorrhages, are well known. Primary disruptive lesions of the brainstem, however, are exceptional. Here we report on clinical and neuroimaging findings, as well as outcome of four male infants with prenatal brainstem disruptions that have been seen between 2005 and 2015. Two infants with extensive brainstem defects (from the midbrain to the medulla) had respiratory insufficiency and died at the age of 12 weeks and 22 months, respectively. Two patients had smaller, unilateral/asymmetrical lesions in the pontomesencephalic and medullary regions, respectively, and presented with permanent multiple cranial nerve deficits and long-tract signs. Recognition of prenatal brainstem disruptions and distinction from malformations are essential for the management and the estimation of a recurrence risk.

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“…Indeed, EZH2 mutation leads to weaver syndrome, an extremely rare congenital disorder with advanced osseous maturation, and distinctive craniofacial, skeletal, and neurological abnormalities (Gibson and others 2012; Imagawa and others 2017; Tatton-Brown and others 2011; Tatton-Brown and others 2013; Weaver and others 1974). Deregulated expression of EZH2 is also found in congenital brainstem disconnection (Barth and others 2017). Besides EZH2, loss-of-function and mutations of EED are suggested as causes for Weaver syndrome (an extremely rare congenital disorder with intellectual disability) and Chiari malformation with neurological problems, respectively (Cooney and others 2017; Imagawa and others 2017; Miro and others 2009).…”

Section: Abnormal Expressions Of Prc2 Members Cause Neurological Disomentioning

confidence: 99%

Polycomb Repressive Complex 2: Emerging Roles in the Central Nervous System

Teng

et al. 2017

Neuroscientist

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The polycomb repressive complex 2 (PRC2) is responsible for catalyzing both di- and trimethylation of histone H3 at lysine 27 (H3K27me2/3). The subunits of PRC2 are widely expressed in the central nervous system (CNS). PRC2 as well as H3K27me2/3, play distinct roles in neuronal identity, proliferation and differentiation of neural stem/progenitor cells, neuronal morphology, and gliogenesis. Mutations or dysregulations of PRC2 subunits often cause neurological diseases. Therefore, PRC2 might represent a common target of different pathological processes that drive neurodegenerative diseases. A better understanding of the intricate and complex regulatory networks mediated by PRC2 in CNS will help to develop new therapeutic approaches and to generate specific brain cell types for treating neurological diseases.

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Deregulated expression of EZH2 in congenital brainstem disconnection

Cited by 7 publications

References 19 publications

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

Prenatal Brainstem Disruptions: Small Lesions–Big Problems

Polycomb Repressive Complex 2: Emerging Roles in the Central Nervous System

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