A5048352010- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- RNA Research and Splicing
- Hemoglobinopathies and Related Disorders
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- Kruppel-like factors research
- Acute Myeloid Leukemia Research
- Erythropoietin and Anemia Treatment
- Cancer-related molecular mechanisms research
- Histone Deacetylase Inhibitors Research
- Iron Metabolism and Disorders
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Signaling Pathways in Disease
- Williams Syndrome Research
- DNA Repair Mechanisms
- interferon and immune responses
- Virus-based gene therapy research
- PARP inhibition in cancer therapy
University of Florida Health
2014-2025
University of Florida
2013-2024
UF Health Cancer Center
2015-2024
Florida College
2001-2016
Foundation for Research and Technology Hellas
2013
University of Crete
2013
Institute of Genetics
2010
Aarhus University
2007
University of Tsukuba
2005
University of Michigan
2005
Abstract Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating post-translational modifications (PTMs), leading to rapid efficient induction of thousands genes involved variety biological processes including...
Proper tissue- and developmental stage-specific transcriptional control over the five genes of human beta-globin locus is elicited in part by region (LCR), but molecular mechanisms that dictate this determined pattern gene expression during development are still controversial. By use homologous recombination yeast to generate mutations LCR within a artificial chromosome (YAC) bearing entire locus, followed injection each mutated YACs into murine ova, we addressed function hypersensitive site...
The inherent properties of DNA as a stable polymer with unique affinity for partner molecules determined by the specific Watson–Crick base pairing makes it an ideal component in self-assembling structures. This has been exploited decades design variety artificial substrates investigations DNA-interacting enzymes. More recently, strategies synthesis more complex two-dimensional (2D) and 3D structures have emerged. However, building such is still progress experiences from different research...
Trithorax proteins and long-intergenic noncoding RNAs are critical regulators of embryonic stem cell pluripotency; however, how they cooperatively regulate germ layer mesoderm specification remains elusive. We report here that HoxBlinc RNA first specifies Flk1(+) then promotes hematopoietic differentiation through regulation hoxb pathways. binds to the genes, recruits Setd1a/MLL1 complexes, mediates long-range chromatin interactions activate transcription genes. Depletion by shRNA-mediated...
Erythropoietin production switches from fetal liver to adult kidney during development. GATA transcription factors 2 and 3 could be involved in modulating this switch, because they were shown negatively regulate erythropoietin gene through a promoter proximal site. Herein, we analyzed the role of several regulation human hepatoma cells. Although GATA-3 expression hepatocytes increases development, mRNA accumulation is unaltered mutant mice lacking GATA-3. We found that GATA-2, -3, -4, -6 are...
HDAC1 and -2 are highly conserved enzymes often coexist in the same coregulator complexes. Understanding regulation of histone deacetylase activities is extremely important because these play key roles epigenetic normal cancer cells. We previously showed that required for glucocorticoid receptor-mediated transcription activation its activity regulated through acetylation by p300 during induction cycle. Here, we HDAC2 also gene activation. HDAC2, however, a different mechanism from HDAC1. not...
The interplay between polycomb and trithorax complexes has been implicated in embryonic stem cell (ESC) self-renewal differentiation. It shown recently that WRD5 Dpy-30, specific components of the SET1/MLL protein complexes, play important roles during ESC differentiation neural lineages. However, not much is known about how where are targeted to genes involved or lineage-specification. Here, we report recruitment hSET1A histone H3K4 methyltransferase (HMT) complex by transcription factor...
The modulation of chromatin structure is a key step in transcription regulation mammalian cells and eventually determines lineage commitment differentiation. USF1/2, Setd1a NURF complexes interact to regulate architecture erythropoiesis, but the mechanistic basis for this hitherto unknown. Here we showed that bind promoters control structural alterations gene activation cell context dependent manner. In human primary erythroid H3K4me3 complex were significantly co-enriched at start sites...
Background A central question in vertebrate transcriptional regulation is how cis ‐regulatory modules, including enhancers, silencers and promoters, communicate with each other over long distances to mandate proper gene expression. In order address this we analysed protein/DNA interactions the human β‐globin locus control region (LCR). One of many proteins that are potentially implicated LCR function Bach1. Bach1 possesses a basic leucine zipper (bZip) domain, as well BTB/POZ domain has been...
The human beta-globin locus control region (LCR) harbors both strong chromatin opening and enhancer activity when assayed in transgenic mice. To understand the contribution of individual DNase I hypersensitive sites (HS) to function LCR, we have mutated core elements within context a yeast artificial chromosome (YAC) carrying entire then analyzed effect these mutations on formation LCR HS expression genes In present study, examined consequences two different HS2 mutations. We first generated...
We explored the mechanism of definitive-stage ɛ-globin transcriptional inactivity within a human β-globin YAC expressed in transgenic mice. focused on globin CAC and CAAT promoter motifs, as previous laboratory clinical studies indicated pivotal role for these elements gene activation. A high-affinity CAC-binding site erythroid krüppel-like factor (EKLF) was placed at position corresponding to that adult promoter, thereby simultaneously ablating direct repeat (DR) element. This mutation led...
Erythroid-specific, high level expression of the beta-globin genes is regulated by locus control region (LCR), composed multiple DNase I-hypersensitive sites and located far upstream genes. Recent studies have shown that LCR core elements recruit RNA polymerase II (pol II). In present study we demonstrate following: 1) pol other basal transcription factors are recruited to hypersensitive elements; 2) dissociates from re-associates with globin gene during replication; 3) interacts but not...
LATS kinase–activating signals selectively modulate CTCF genomic occupancy and 3D genome organization.
Atrial natriuretic factor (ANF) is abundantly expressed in atrial cardiomyocytes throughout ontogeny and ventricular the developing heart. However, during cardiac failure hypertrophy, ANF expression can reappear adult cardiomyocytes. The transcription Nkx2-5 one of major transactivators gene We identified binding at three 5′ regulatory elements (kb −34, −31, −21) proximal promoter by ChIP assay using neonatal mouse 3C analysis revealed close proximity between distal region. A 5.8-kb fragment...
HDAC1-containing NuRD complex is required for GATA-1-mediated repression and activation.GATA-1 associated with acetylated complex, which has no deacetylase activity, gene activation.Acetylated HDAC1 converts from a repressor to an activator during GATA-1-directed erythroid differentiation program.HDAC1 acetylation may function as master regulator the activity of containing complexes. Histone deacetylases (HDACs) play important roles in regulating cell proliferation differentiation. The...
We report the genomic occupancy profiles of key hematopoietic transcription factor GATA-1 in pro-erythroblasts and mature erythroid cells fractionated from day E12.5 mouse fetal liver cells. Integration with available genome-wide epigenetic assayed enabled as to evaluate involvement modulating local chromatin structure target genes during differentiation. Our results suggest that associates preferentially changes specific modifications, such H4K16, H3K27 acetylation H3K4 di-methylation....