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[Sperm chromatin structure assay versus sperm chromatin dispersion test in detecting sperm DNA integrity and correlation of sperm DNA fragmentation with semen parameters].

OBJECTIVE: Sperm DNA fragmentation (SDF) is widely used to predict male infertility and the methods of detecting SDF are varied. This study aimed to compare two methods of SDF detection and investigate the correlation between SDF and sperm quality. METHODS: Using sperm chromatin structure assay (SCSA) and sperm chromatin dispersion test (SCD), we detected SDF in 108 semen samples collected in the Center of Reproduction and Genetics of Suzhou Municipal Hospital. We compared the results of the two methods and analyzed the correlations of SDF routine semen parameters, sperm morphology and the ag…

CHD4 is a copper sensor linking chromatin remodeling to cuproptosis.

Cuproptosis is a copper-dependent regulated cell death pathway, but its connection to chromatin regulation is poorly understood. Here, we demonstrate that cuproptosis-sensitive tumor cells exhibit an "epigenetically primed" state with elevated chromatin accessibility and active histone marks. Multi-omics analyses reveal extensive chromatin reprogramming, including topologically associating domain (TAD) fusion and global reduction of enhancer-associated loops. We identify the chromatin remodeler CHD4, a core subunit of the NuRD complex, as a direct copper sensor. Copper ions bind to the CXXC do…

Therapeutic targeting of chromatin alterations in leukemia and solid tumors.

Alterations in chromatin conformation and post-translational modification of histones have become increasingly recognized as critical drivers of cancer development, progression, and therapy resistance. Recent advances in drug development have led to the establishment of several highly selective small molecule inhibitors, several of which are currently under investigation in clinical trials. These compounds allow the precise interrogation of specific chromatin features and functions, transforming the field of epigenetic cancer therapy from rather unselective approaches, like histone deacetylase…

Epigenetic alterations in prostate cancer: the role of chromatin remodeling.

Prostate cancer (PCa) is one of the most common cancers in men, distinguished by a multifaceted pathogenesis that involves substantial epigenetic modifications. This article emphasizes the critical role of chromatin remodeling in PCa advancement. Chromatin remodeling, a key epigenetic mechanism, influences gene expression by modulating the chromatin structure through the action of specialized complexes such as SWI/SNF, ISWI, CHD, & INO80, thereby regulating genes vital to tumor progression. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus databases for s…

DNA methylation landscapes in human cells and their chromatin determinants.

Acetaminophen (APAP) overdose is a clinically relevant model of drug hepatotoxicity and acute liver failure. After decades of research, many aspects of the mechanism of APAP-induced liver injury are well established. These include the cytochrome P450 2E1-mediated formation of a reactive metabolite, hepatic glutathione depletion, mitochondrial protein adduct formation with oxidant stress and peroxynitrite formation, iron-catalyzed protein nitration in mitochondria, the opening of the mitochondrial permeability transition pore, and release of mitochondrial intermembrane proteins including endonu

Chromatin and epigenetic regulation in malignant tumors: A comprehensive review.

Epigenetics and chromatin biology have been two distinct research fields for many years. There is a close relationship between epigenetics and chromatin biochemistry, and the dynamic changes of chromatin serve as an important basis for epigenetic regulation. The relationship between epigenetics and chromatin is reflected in the dynamic changes and structural adjustments of chromatin. In this article, we focus on previously underappreciated chromatin remodeling proteins. This review summarizes the biological significance of chromatin remodeling complexes in malignancies, including the physiolog…

FBRSL1 regulates the expression of chromatin regulators BRPF1 and KAT6A.

FBRSL1-associated syndrome is a rare congenital malformation and intellectual disability syndrome caused by heterozygous truncating variants in Fibrosin-Like 1 (FBRSL1). While FBRSL1 is known to be involved in embryonic development, its precise molecular function remains poorly understood. Therefore, the aim of this study was to elucidate the molecular function of FBRSL1, which is thought to be essential for developmental processes, and to investigate the effect of patient-derived truncating FBRSL1 variants. Using chromatin immunoprecipitation followed by sequencing (ChIP-Seq), we show that FB…

Chromatin accessibility and gene expression in the parasite Trichomonas vaginalis.

Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes more than 270 million infections annually. The infect … ely understood. While many studies have reported a positive correlation between gene expression and chromatin accessibility in other cells, this relationship has not been analyzed in T. vaginalis. To address these questions, we selected two contrasting T. vaginalis strains based on their interactions with host cells: the B7268 strain, a highly adherent one …

Deciphering the role of Hat1 in spermatogenesis: Chromatin organization and beyond.

Spermatogenesis, a core process for male fertility, relies heavily on chromatin organization regulated by histone acetyltransferases (HATs). However, the spatiotemporal expression pattern of histone acetyltransferase 1 (Hat1) in mouse testes and its specific role in spermatogenesis via chromatin organization remain unclear. This study employed RT-qPCR, Western blot, immunofluorescence localization, and bioinformatics to explore Hat1's dynamic expression and regulatory mechanisms during mouse spermatogenesis. Results showed that both Hat1 mRNA and protein were significantly upregulated in the t…

Hungry for control: metabolite signaling to chromatin in Plasmodium falciparum.

The human malaria parasite Plasmodium falciparum undergoes a complex life cycle in two hosts, mammalian and mosquito, where it is constantly subjected to environmental changes in nutrients. Epigenetic mechanisms govern transcriptional switches and are essential for parasite persistence and proliferation. Parasites infecting red blood cells are auxotrophic for several nutrients, and mounting evidence suggests that various metabolites act as direct substrates for epigenetic modifications, with their abundance directly relating to changes in parasite gene expression. Here, we review the latest un

Phosphoinositide signaling in the nucleus: Impacts on chromatin and transcription regulation.

Phosphoinositides also called Polyphosphoinositides (PPIns) are small lipid messengers with established key roles in organelle trafficking and cell signaling in response to physiological and environmental inputs. Besides their well-described functions in the cytoplasm, accumulating evidences pointed to PPIns involvement in transcription and chromatin regulation. Through the description of previous and recent advances of PPIns implication in transcription, this review highlights key discoveries on how PPIns modulate nuclear factors activity and might impact chromatin to modify gene expression. …

Role of chromatin modulator Dpy30 in osteoclast differentiation and function.

Osteoclasts are the principal bone resorption cells crucial for homeostatic bone remodeling and pathological bone destruction. Increasing data demonstrate a vital role of histone methylation in osteoclastogenesis. As an integral core subunit of H3K4 methyltransferases, Dpy30 is notal as a key chromatin regulator for cell growth and differentiation and stem cell fate determination, particularly in the hematopoietic system. However, its role in osteoclastogenesis is currently unknown. Herein, we generated Dpy30F/F; LysM-Cre+/+ mice, which deletes Dpy30 in myeloid cells, to characterize its invol…

Chromatin compartment dynamics in a haploinsufficient model of cardiac laminopathy.

Mutations in A-type nuclear lamins cause dilated cardiomyopathy, which is postulated to result from dysregulated gene expression due to changes in chromatin organization into active and inactive compartments. To test this, we performed genome-wide chromosome conformation analyses in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with a haploinsufficient mutation for lamin A/C. Compared with gene-corrected cells, mutant hiPSC-CMs have marked electrophysiological and contractile alterations, with modest gene expression changes. While large-scale changes in chromosomal top…

Infection Reveals a Modification of SIRT2 Critical for Chromatin Association.

Sirtuin 2 is a nicotinamide-adenine-dinucleotide-dependent deacetylase that regulates cell processes such as carcinogenesis, cell cycle, DNA damage, and infection. Subcellular localization of SIRT2 is crucial for its function but is poorly understood. Infection with the bacterial pathogen Listeria monocytogenes, which relocalizes SIRT2 from the cytoplasm to the chromatin, provides an ideal stimulus for the molecular study of this process. In this report, we provide a map of SIRT2 post-translational modification sites and focus on serine 25 phosphorylation. We show that infection specifically i…

BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin.

Bromodomain protein 4 (BRD4) is a chromatin-binding protein implicated in cancer and autoimmune diseases that functions as a scaffold for transcription factors at promoters and super-enhancers. Although chromatin decompaction and transcriptional activation of target genes are associated with BRD4 binding, the mechanisms involved are unknown. We report that BRD4 is a histone acetyltransferase (HAT) that acetylates histones H3 and H4 with a pattern distinct from those of other HATs. Both mouse and human BRD4 have intrinsic HAT activity. Importantly, BRD4 acetylates H3 K122, a residue critical fo…

Механика вирусного Хроматина открывает прессу человеческого аденовируса.

Тщательное содержание обнаженных геномов в некоторых вирусах приводит к высокому внутреннему давлению, которое облегчает их перенос в хозяин. Аденовирус, однако, кодирует гистонеподобные белки, которые ассоциируются с его геномомом, что приводит к замкнутому конденсату ДНК-протеина (core). Клейф этих белков во время созревания уменьшает конденсацию ядра и расщепляет вирион для надлежащего отсоединения с помощью неопознанных механизмов. Здесь мы открываем отдельные, зрелые и незрелые аденовирусные клетки для непосредственного изучения механики их хроматиновых ядер. Мы находим незрелые ядра боле

Совпадение в аннотации оригинала
Tight confinement of naked genomes within some viruses results in high internal pressure that facilitates their translocation into the host. … e we open individual, mature and immature adenovirus cages to directly probe the mechanics of their chromatin-like cores. We find that immature cores are more rigid than the mature ones, unveiling a mechanical signature of their condensation level. Conversely, intact mature particles demonstrate more rigidity than immature or empty ones. DNA-condensing poly …

Chromatin modifiers and the promise of epigenetic therapy in acute leukemia.

Hematopoiesis is a tightly regulated process involving the control of gene expression that directs the transition from hematopoietic stem an … of transcriptional regulators and the proliferative signaling pathways are ultimately influenced by chromatin structure. Candidate gene, whole-genome and whole-exome sequencing studies have identified recurrent somatic mutations in genes encoding epigenetic modifiers in both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). In contrast to the …

Neuronal necrosis is regulated by a conserved chromatin-modifying cascade.

Neuronal necrosis induced by calcium overload causes devastating brain dysfunction in diseases such as stroke and brain trauma. It has been … in vitro and in vivo. Together, our research demonstrates that neuronal necrosis is regulated by a chromatin-modifying cascade, and this discovery may provide potential therapeutic targets and biomarkers for neuronal necrosis.

Chromatin dynamics and the repair of DNA double strand breaks.

DNA double-strand breaks (DSBs) arise through both replication errors and from exogenous events such as exposure to ionizing radiation. DSBs are potentially lethal, and cells have evolved a highly conserved mechanism to detect and repair these lesions. This mechanism involves phosphorylation of histone H2AX (γH2AX) and the loading of DNA repair proteins onto the chromatin adjacent to the DSB. It is now clear that the chromatin architecture in the region surrounding the DSB has a critical impact on the ability of cells to mount an effective DNA damage response. DSBs promote the direct the forma…