ProA and ProB repeat sequences shape genome organization, and enhancers open domains DOI

Konstantinn Bonnet,

Nicolas Hulo, Raphaël Mourad

и другие.

Опубликована: Окт. 29, 2023

SUMMARY There is a growing awareness that repeat sequences (RepSeq) - the main constituents of human genome are also prime players in its organization. Here we propose should be envisioned as supersystem with three subsystems, each composed functionally redundant, cooperating elements. We define herein ProA and ProB RepSeqs promote either A/euchromatin or B/heterochromatin compartment. shape A/B partitioning, such relative proportions determine propensity chromosome segment to adopt an A B configuration. In human, core essentially made Alu elements, whereas consist young L1 some Endogenous Retroviruses (ERVs) well panel AT-rich microsatellites pericentromeric telomeric satellites. Additionally, more indefinite character and, importantly, their derivatives known “transcriptional enhancers”, can shift between functions thus act open close specific chromatin domains depending on cellular context. this framework, genes promoters appear special class that, active, transcribed state, reinforce openness surroundings. Molecular mechanisms involve cooperativity presumably underpinned by condensate-like properties heterochromatin, which elements oppose several ways. provide strong arguments altered CpG methylation patterns cancer including marked loss compartment, result primarily from global imbalance process erasure. Our results suggest resulting impaired function globally weaken rendering it plastic, turn may confer fate plasticity cell.

Язык: Английский

The transcriptomic landscape of spinal V1 interneurons reveals a role for En1 in specific elements of motor output DOI Creative Commons

Alexandra J. Trevisan,

Katie Han, Phillip Chapman

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 19, 2024

SUMMARY Neural circuits in the spinal cord are composed of diverse sets interneurons that play crucial roles shaping motor output. Despite progress revealing cellular architecture cord, extent cell type heterogeneity within interneuron populations remains unclear. Here, we present a single-nucleus transcriptomic atlas V1 across postnatal development. We find core molecular taxonomy distinguishing neonatal perdures into adulthood, suggesting conservation function Moreover, identify key role for En1, transcription factor marks population, specifying one unique subset Pou6f2 interneurons. Loss En1 selectively disrupts frequency rhythmic locomotor output but does not disrupt flexion/extension limb movement. Beyond serving as resource this neuronal our study highlights how deep profiling provides an entry point functional studies specialized types

Язык: Английский

Процитировано

4
Disabling leading and lagging strand histone transmission results in parental histones loss and reduced cell plasticity and viability DOI Creative Commons
Leonie Kollenstart, Alva Biran, Nicolás Alcaraz

и другие.

Science Advances, Год журнала: 2025, Номер 11(8)

Опубликована: Фев. 19, 2025

In the process of DNA replication, first steps in restoring chromatin landscape involve parental histone recycling and new deposition. Disrupting to either leading or lagging strand induces asymmetric inheritance, affecting epigenome maintenance cellular identity. However, order kinetics these effects remain elusive. Here, we use inducible mutants dissect early late consequences impaired recycling. Simultaneous disruption both (POLE4) (MCM2-2A) pathways impairs transmission histones newly synthesized DNA, releasing some soluble pool. Subsequently, H3K27me3 accumulates aberrantly during restoration a manner preceding gene expression changes. Loss inheritance ensuing defects alter embryonic stem cells challenge differentiation programs cell viability. Our findings demonstrate importance efficient histone-based information replication for maintaining landscapes, potential,

Язык: Английский

Процитировано

0
Small molecule compounds targeting G9a/GLP: Recent advances and perspectives DOI
Qiangsheng Zhang, Li Lu,

Siyan Li

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 117525 - 117525

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Clinical impact and in vitro characterization of ADNP variants in pediatric patients DOI Creative Commons

Chuanhui Ge,

Yuxin Tian,

Chunchun Hu

и другие.

Molecular Autism, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 22, 2024

Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it also called ADNP syndrome. multitasking protein with function as transcription factor, playing critical role brain development. Furthermore, have been identified one of most common single-gene causes autism spectrum (ASD) and intellectual disability. We assembled cohort 15 Chinese pediatric patients, 13 coding region gene, evaluated their clinical phenotypes. Additionally, we constructed corresponding performed western blotting immunofluorescence analysis to examine expression subcellular localization human HEK293T SH-SY5Y cells. Our study conducted thorough characterization manifestations children variants, revealed broad symptoms including global developmental delay, disability, ASD, facial abnormalities, other features. In vitro studies were carried out check variants. Two cases presented missense while remainder exhibited nonsense or frameshift leading truncated mutants overexpression systems. Both overexpressed wildtype all different found be confined nuclei cells; however, distinctive pattern nuclear bodies formed was either partially entirely disrupted mutant proteins. Moreover, two p.Y719* on signal (NLS) pattern, predominantly manifesting cytoplasm limited relatively small sample size absence longitudinal framework monitor progression patient conditions over time. lacked vivo evidence further indicate causal implications reported first HVDAS patients population provided systematic presentations laboratory examinations. multiple validated them vitro. findings offered valuable insights into diverse associated HVDAS.

Язык: Английский

Процитировано

3
Effects of microgravity on neural crest stem cells DOI Creative Commons
Yilin Han, Povilas Barasa, Lukas Zeger

и другие.

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 27, 2024

Exposure to microgravity (μg) results in a range of systemic changes the organism, but may also have beneficial cellular effects. In previous study we detected increased proliferation capacity and upregulation genes related survival boundary cap neural crest stem cells (BC) after MASER14 sounding rocket flight compared ground-based controls. However, whether these were due μg or hypergravity was not clarified. current MASER15 experiment BCs exposed simultaneously 1 g conditions provided by an onboard centrifuge. displayed markedly on board controls, genetic analysis harvested 5 h revealed upregulation, specifically μg-exposed BCs, Zfp462 transcription factor, key regulator cell pluripotency neuronal fate. This associated with alterations exosome microRNA content between specimens. Since specimens from obtained for week's delay, examined gene expression different experiments, which flight. The overall pattern down-regulated BC directly (MASER15). MicroRNA altered medium delay collected samples. conclusion, our indicates that even short exposure alters expression, leading survival, lasting long time exposure. With delayed harvest specimens, situation occur special post-flight circumstances, is modified fast specimen harvest, direct effects be partially attenuated, whereas other can last return ground conditions.

Язык: Английский

Процитировано

2
Dominant-negative variants in CBX1 cause a neurodevelopmental disorder DOI Creative Commons
Yukiko Kuroda, Aiko Iwata‐Otsubo, Kerith‐Rae Dias

и другие.

Genetics in Medicine, Год журнала: 2023, Номер 25(7), С. 100861 - 100861

Опубликована: Апрель 20, 2023

Язык: Английский

Процитировано

6
Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants DOI

Lu Qiao,

Carrie L. Welch, Rebecca Hernan

и другие.

The American Journal of Human Genetics, Год журнала: 2024, Номер 111(11), С. 2362 - 2381

Опубликована: Сен. 26, 2024

Язык: Английский

Процитировано

1
miR-377-3p Regulates Hippocampal Neurogenesis via the Zfp462-Pbx1 Pathway and Mediates Anxiety-Like Behaviors in Prenatal Hypoxic Offspring DOI
Bin Wang, Yichen Zhu, Bin Wei

и другие.

Molecular Neurobiology, Год журнала: 2023, Номер 61(4), С. 1920 - 1935

Опубликована: Окт. 11, 2023

Язык: Английский

Процитировано

2
Seven Novel Variants of Weiss‐Kruszka Syndrome and Phenotype Expansion DOI Creative Commons

Anna Hau,

Anne Baxter,

Kate Chandler

и другие.

American Journal of Medical Genetics Part A, Год журнала: 2024, Номер unknown

Опубликована: Сен. 17, 2024

ABSTRACT Weiss‐Kruszka syndrome (WKS) is a rare genetic disorder characterized by metopic ridging, ptosis, arched eyebrows, down slanting palpebral fissures, abnormalities in the corpus callosum, cardiac malformations, and variable neurodevelopmental delay. To date, 32 individuals with diagnosis of WKS have been reported literature. The caused heterozygous pathogenic variant ZNF462 gene or deletion 9p31.2 region involving . There significant phenotypic heterogeneity intrafamilial variability among these patients. Our study reviewed nine patients from seven unrelated families identified novel variants through exome sequencing. GestaltMatcher analysis our cohort's facial images, alongside previously published images patients, demonstrated high degree similarity. Further longitudinal research needed to delineate this condition's long‐term health implications adult‐onset features.

Язык: Английский

Процитировано

0
Analysis of clinical phenotypes and genetic variations in two pedigrees affected with Weiss–Kruszka syndrome DOI Creative Commons

Chunxiao Han,

Changshui Chen, Yuxin Zhang

и другие.

BMC Medical Genomics, Год журнала: 2024, Номер 17(1)

Опубликована: Ноя. 5, 2024

Weiss-Kruszka syndrome (WSKA) is a rare autosomal dominant characterized by multiple congenital anomalies caused variants in the zinc finger protein 462 gene (ZNF462). About 40 cases of have been reported worldwide, and aim this study was to investigate genetic causes three patients from two family pedigrees with accumulating more data on disease. To explore clinical characteristics Weiss–Kruszka syndrome. The history members were collected, pathogenic genes analysed whole-exon sequencing. Suspicious verified Sanger sequencing verification bioinformatics prediction. Proband 1 has developmental delay, autistic behaviour, abnormal electroencephalogram results. WES revealed classical heterozygous c.6696–2 A > C splice variant ZNF462 gene, which detected neither parent. This position conserved, predicted be deleterious. Minigene assays that types aberrantly spliced mRNAs produced. MRI proband 2 suggested dysplasia corpus callosum formation hemispheric cleft cysts, teardrop-like appearance lateral ventricle. c.4891 T:p. Glu1631Ter nonsense inherited her mother. According guidelines American Society Medical Genetics combined its manifestations, determined possible variant. c.6696-2 A>C c.4891C T:p.Glu1631Ter likely underlies children (foetus), enriches spectrum Chinese provides basis for prenatal diagnosis counselling.

Язык: Английский

Процитировано

0