The histone variant H2A.Z is involved in several processes such as transcriptional control, DNA repair, regulation of centromeric heterochromatin and, not surprisingly, is implicated in diseases such as cancer. Here, we review the recent developments on H2A.Z focusing on its role in transcriptional activation and repression. H2A.Z, as a replication-independent histone, has been studied in several model organisms and inducible mammalian model systems. Its loading machinery and several modifying enzymes have been recently identified, and some of the long-standing discrepancies in transcriptional activation and/or repression are about to be resolved. The buffering functions of H2A.Z, as supported by genome-wide localization and analyzed in several dynamic systems, are an excellent example of transcriptional control. Posttranslational modifications such as acetylation and ubiquitination of H2A.Z, as well as its specific binding partners, are in our view central players in the control of gene expression. Understanding the key-mechanisms in either turnover or stabilization of H2A.Z-containing nucleosomes as well as defining the H2A.Z interactome will pave the way for therapeutic applications in the future.
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http://dx.doi.org/10.1186/s13072-019-0274-9 | DOI Listing |
Int J Mol Sci
December 2024
Department of Oral and Maxillofacial Plastic Surgery, Faculty of Medicine, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression.
View Article and Find Full Text PDFMedicina (Kaunas)
November 2024
Respiratory Disease Unit, University Hospital of Modena, 41124 Modena, Italy.
Recent advances in genetics and epigenetics have provided critical insights into the pathogenesis of both idiopathic and non-idiopathic interstitial lung diseases (ILDs). Mutations in telomere-related genes and surfactant proteins have been linked to familial pulmonary fibrosis, while variants in MUC5B and TOLLIP increase the risk of ILD, including idiopathic pulmonary fibrosis and rheumatoid arthritis-associated ILD. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs such as miR-21 and miR-29, regulate fibrotic pathways, influencing disease onset and progression.
View Article and Find Full Text PDFEur J Paediatr Neurol
December 2024
Department of Pediatrics, Peking University People's Hospital, Beijing, China; Epilepsy Center, Peking University People's Hospital, Beijing, China. Electronic address:
Aim: Exploring the association between SETD1B variants and absence seizures (ASs).
Methods: We engaged a small cohort of four pediatric epilepsy patients with identified SETD1B variants and conducted a comprehensive review of 50 documented instances. Clinical profiles were meticulously compiled, and genetic screening was executed via trio-based whole-exome sequencing.
Front Mol Neurosci
December 2024
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States.
Post-transcriptional mechanisms, such as alternative splicing and polyadenylation, are recognized as critical regulatory processes that increase transcriptomic and proteomic diversity. The advent of next-generation sequencing and whole-genome analyses has revealed that numerous transcription and epigenetic regulators, including transcription factors and histone-modifying enzymes, undergo alternative splicing, most notably in the nervous system. Given the complexity of regulatory processes in the brain, it is conceivable that many of these splice variants control different aspects of neuronal development.
View Article and Find Full Text PDFThe chromatin of the centromere provides the assembly site for the mitotic kinetochore that couples microtubule attachment and force production to chromosome movement in mitosis. The chromatin of the centromere is specified by nucleosomes containing the histone H3 variant CENP-A. The constitutive centromeric-associated network (CCAN) and kinetochore are assembled on CENP-A chromatin to enable chromosome separation.
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