A5061496028- Hemoglobinopathies and Related Disorders
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Blood groups and transfusion
- Erythropoietin and Anemia Treatment
- DNA Repair Mechanisms
- Iron Metabolism and Disorders
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- Pancreatic function and diabetes
- Blood disorders and treatments
- Blood properties and coagulation
- Congenital heart defects research
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
University of Milano-Bicocca
2012-2024
University of Milan
1993-2013
University of Modena and Reggio Emilia
2012
The San Raffaele Telethon Institute for Gene Therapy
2010
Istituti di Ricovero e Cura a Carattere Scientifico
2010
Vita-Salute San Raffaele University
2010
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2004
University of Trieste
2004
Consorzio Interuniversitario per le Biotecnologie
2004
New York Blood Center
1990-1993
RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). The RBP FUS is implicated in RNA metabolism and repair, it undergoes reversible liquid-liquid phase separation (LLPS) vitro. Here, we demonstrate that FUS-dependent LLPS necessary for initiation DDR. Using laser microirradiation FUS-knockout cells, show required recruitment to sites DDR factors KU80, NBS1, 53BP1 SFPQ, another relocation SFPQ similarly impaired by inhibitors, or...
The transcription factor Sox2 is active in neural stem cells, and Sox2`knockdown' mice show defects stem/progenitor cells the hippocampus eye, possibly some neurons. In humans, heterozygous deficiency associated with eye abnormalities, hippocampal malformation epilepsy. To better understand role of Sox2, we performed vitro differentiation studies on cultured from embryonic adult brains `knockdown' mutants. expression high undifferentiated declines differentiation, but remains visible at...
The Sox2 transcription factor is expressed early in the stem cells of blastocyst inner cell mass and, later, neural cells. We previously identified a 5'-regulatory region directing transgene expression to and precursors forebrain. Here, we identify core enhancer element able specify forebrain mouse embryos, show that same efficiently activates mass-derived embryonic (ES) Mutation POU binding sites, recognize factors Brn1 Brn2, shows these sites contribute activity are also essential for ES...
Journal Article The effects of HPFH mutations in the human γ-globin promoter on binding ubiquitous and erythroid specific nuclear factors Get access R. Mantovani, Mantovani Dipartimento di Genetica e Biologia dei Microrganismi, Università Milano Studio MilanMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Malgaretti, Malgaretti S. Nicolis, Nicolis A. Ronchi, Ronchi B. Giglioni, Giglioni 1Centro per lo della Patologia Cellulare del CNRMilan,...
Both light and developmental stimuli are directly involved in the regulation of plant gene expression. In maize, activation anthocyanin pathway represents an excellent model system for studying interactions between external factor, such as light, internal factors that regulate seed development. By analyzing detail aleurone pericarp layers, different windows have been found two tissues[mdash]the former advanced stages development latter early Transcriptional control structural genes...
Journal Article CCAAT-box binding protein NF-Y (CBF, CP1)recognizes the minor groove and distorts DNA Get access Antonella Ronchi, Ronchi Search for other works by this author on: Oxford Academic PubMed Google Scholar Marianna Bellorini, Bellorini Nicola Mongelli, Mongelli 1Pharmacia/Farmitalia Carlo Erba, Nerviano Research CenterVia Papa Giovanni XXIII 68, 20014 Nerviano, Italy Roberto Mantovani * *To whom correspondence should be addressed Nucleic Acids Research, Volume 23, Issue 22, 25...
The transcription factor GATA-1 is expressed in a subset of hemopoietic cells, where it mediates the celltype specific expression several genes. We have cloned mouse and human A region upstream to first exon, highly conserved between man, acts as an erythroid enhancer transient assays, if linked or SV40 promoter. activity almost completely dependent on integrity dimeric binding site.
The activity of transcription factors is tightly modulated by posttranslational modifications affecting stability, localization, and protein–protein interactions. Conjugation to SUMO a reversible modification that has been shown regulate important involved in cell proliferation, differentiation, tumor suppression. Here, we demonstrate the erythroid factor GATA-1 sumoylated vitro vivo map single lysine residue SUMO-1 attachment. We show nuclear RING finger protein PIASy promotes sumoylation...
The transcriptional binding protein NFE-1 (also called GF-1 and Ery-f1) is thought to play a necessary, but not sufficient, role in the regulation of differentiation- related gene expression subset hematopoietic lineages (erythroid, megakaryocytic, basophil-mast cell).In order clarify mechanism which underlies lineage-specificity expression, as well relationship between this factor growth responsiveness, we have evaluated capacity erythropoietin (Epo)-, granulo- monocytic (GM)-colony...
The -198 T----C mutation in the promoter of A gamma-globin gene increases 20-30 fold expression this adult erythroid cells patients (Hereditary Persistence Fetal Hemoglobin, HPFH). We show here that creates a strong binding site, resembling CACCC box, for two ubiquitous nuclear proteins, one which is Sp1. mutated four to five-fold more efficient than normal driving CAT reporter plasmid when transfected into cells. overexpression mutant abolished by introduction an additional disrupting new...
Defects in genes encoding ribosomal proteins cause Diamond Blackfan Anemia (DBA), a red cell aplasia often associated with physical abnormalities. Other bone marrow failure syndromes have been attributed to defects components but the link between erythropoiesis and ribosome remains be fully defined. Several lines of evidence suggest that synthesis lead "ribosomal stress" p53 activation either cycle arrest or induction apoptosis. Pathways independent also proposed play role DBA pathogenesis....
The transcription factor Sox2 is essential for neural stem cells (NSC) maintenance in the hippocampus and vitro . Emx2 also critical hippocampal development NSC self-renewal. Searching 'modifier' genes affecting deficiency phenotype mouse, we observed that loss of one allele substantially increased telencephalic β-geo (LacZ) expression a transgene driven by 5′ or 3′ enhancer. Reciprocally, overexpression cultures inhibited activity same transgene. In vivo , levels medial wall, including...
The -175 T▸C mutation in the promoter of Aγ- Gor γ-globin gene causes a 50-100 fold increase expression respective adult erythroid cells (Hereditary Persistence Fetal Hemoglobin). We show here that this increases 3-9 γ-CAT reporter plasmid transfected into K562, but not same non cells. overexpression mutant is abolished by binding site for specific factor NFE1; inactivation adjacent ubiquitous OTF1 does cause normal promoter. Previous results demonstrated slightly vitro NFE1 and almost...
The CCAAT-binding activator NF-Y is formed by three evolutionary conserved subunits, two of which contain putative histone-like domains. We investigated binding to all CCAAT boxes globin promoters in direct binding, competition, and supershift electrophoretic mobility shift assay; we found that the α, ζ, proximal γ human prosimian Galago bind avidly, distal have intermediate affinity, whereas ε β sequences very poorly. developed an efficientin vitro transcription system from erythroid K562...
Naturally occurring nondeletional mutations affecting the distal CCAAT box of human γ-globin gene promoter result in hereditary persistence fetal hemoglobin adult life. Although is target several factors, including CP1/NFY, CDP, GATA-1 and NFE3, only NFE3 binding activity consistently sensitive to well characterized this region such as G−117 → A, C−114 T, Δ13 hemoglobin. We extensively specificities demonstrated that has unique properties with respect other box-binding proteins....
We observed that binding sites for the ubiquitously expressed transcription factor CP2 were present in regulatory regions of multiple erythroid genes. In these regions, site was adjacent to a GATA-1. Using three such (from genes encoding factors GATA-1, EKLF, and p45 NF-E2), we demonstrated functional importance CP2/GATA-1 sites. particular, binds GATA-1 HS2 enhancer, generating ternary complex with DNA. Mutations consensus greatly impaired activity transient transfection assays K562 cells....