Role of GATA-1 in ?-globin locus chromatin structure reorganization and eryrhoid [i.e. erythroid] gene expression.

2004 ◽  
Author(s):  
Michael E. Layon
Keyword(s):  
Gene Expression ◽  
Chromatin Structure

Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation

1991 ◽  
Vol 11 (1) ◽  
pp. 47-54
Author(s):  
H Chan ◽  
S Hartung ◽  
M Breindl
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chromatin Structure ◽  
Transcriptional Activity ◽  
Xenopus Laevis Oocytes ◽  
Regulatory Sequences ◽  
Type I ◽  
Wild Type ◽  
Col1a1 Gene

We have studied the role of DNA methylation in repression of the murine alpha 1 type I collagen (COL1A1) gene in Mov13 fibroblasts. In Mov13 mice, a retroviral provirus has inserted into the first intron of the COL1A1 gene and blocks its expression at the level of transcriptional initiation. We found that regulatory sequences in the COL1A1 promoter region that are involved in the tissue-specific regulation of the gene are unmethylated in collagen-expressing wild-type fibroblasts and methylated in Mov13 fibroblasts, confirming and extending earlier observations. To directly assess the role of DNA methylation in the repression of COL1A1 gene transcription, we treated Mov13 fibroblasts with the demethylating agent 5-azacytidine. This treatment resulted in a demethylation of the COL1A1 regulatory sequences but failed to activate transcription of the COL1A1 gene. Moreover, the 5-azacytidine treatment induced a transcription-competent chromatin structure in the retroviral sequences but not in the COL1A1 promoter. In DNA transfection and microinjection experiments, we found that the provirus interfered with transcriptional activity of the COL1A1 promoter in Mov13 fibroblasts but not in Xenopus laevis oocytes. In contrast, the wild-type COL1A1 promoter was transcriptionally active in Mov13 fibroblasts. These experiments showed that the COL1A1 promoter is potentially transcriptionally active in the presence of proviral sequences and that Mov13 fibroblasts contain the trans-acting factors required for efficient COL1A1 gene expression. Our results indicate that the provirus insertion in Mov13 can inactivate COL1A1 gene expression at several levels. It prevents the developmentally regulated establishment of a transcription-competent methylation pattern and chromatin structure of the COL1A1 domain and, in the absence of DNA methylation, appears to suppress the COL1A1 promoter in a cell-specific manner, presumably by assuming a dominant chromatin structure that may be incompatible with transcriptional activity of flanking cellular sequences.

The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme

2008 ◽  
Vol 389 (4) ◽  
pp. 323-331 ◽  
Author(s):  
David Umlauf ◽  
Peter Fraser ◽  
Takashi Nagano
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Chromatin Structure ◽  
Genome Architecture ◽  
Paradoxical Situation ◽  
Intergenic Regions ◽  
Non Coding Rnas ◽  
Variations On A Theme

Abstract Transcriptome studies have uncovered a plethora of non-coding RNAs (ncRNA) in mammals. Most originate within intergenic regions of the genome and recent evidence indicates that some are involved in many different pathways that ultimately act on genome architecture and gene expression. In this review, we discuss the role of well-characterized long ncRNAs in gene regulation pointing to their similarities, but also their differences. We will attempt to highlight a paradoxical situation in which transcription is needed to repress entire chromosomal domains possibly through the action of ncRNAs that create nuclear environments refractory to transcription.

scholarly journals Slowing Down Ageing: The Role of Nutrients and Microbiota in Modulation of the Epigenome

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1251 ◽  
Author(s):  
Agnieszka Gadecka ◽  
Anna Bielak-Zmijewska
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Structural Changes ◽  
Epigenetic Modification ◽  
Condensed Chromatin ◽  
Gene Promoters ◽  
Methylation Of Dna ◽  
Age Related ◽  
Altered Gene

The human population is getting ageing. Both ageing and age-related diseases are correlated with an increased number of senescent cells in the organism. Senescent cells do not divide but are metabolically active and influence their environment by secreting many proteins due to a phenomenon known as senescence associated secretory phenotype (SASP). Senescent cells differ from young cells by several features. They possess more damaged DNA, more impaired mitochondria and an increased level of free radicals that cause the oxidation of macromolecules. However, not only biochemical and structural changes are related to senescence. Senescent cells have an altered chromatin structure, and in consequence, altered gene expression. With age, the level of heterochromatin decreases, and less condensed chromatin is more prone to DNA damage. On the one hand, some gene promoters are easily available for the transcriptional machinery; on the other hand, some genes are more protected (locally increased level of heterochromatin). The structure of chromatin is precisely regulated by the epigenetic modification of DNA and posttranslational modification of histones. The methylation of DNA inhibits transcription, histone methylation mostly leads to a more condensed chromatin structure (with some exceptions) and acetylation plays an opposing role. The modification of both DNA and histones is regulated by factors present in the diet. This means that compounds contained in daily food can alter gene expression and protect cells from senescence, and therefore protect the organism from ageing. An opinion prevailed for some time that compounds from the diet do not act through direct regulation of the processes in the organism but through modification of the physiology of the microbiome. In this review we try to explain the role of some food compounds, which by acting on the epigenetic level might protect the organism from age-related diseases and slow down ageing. We also try to shed some light on the role of microbiome in this process.

scholarly journals Chromatin is an ancient innovation conserved between Archaea and Eukarya

eLife ◽  
2012 ◽  
Vol 1 ◽  
Author(s):  
Ron Ammar ◽  
Dax Torti ◽  
Kyle Tsui ◽  
Marinella Gebbia ◽  
Tanja Durbic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Nucleosome Occupancy ◽  
Regulation Of Gene Expression ◽  
Haloferax Volcanii ◽  
Dna Compaction ◽  
Genome Wide ◽  
Eukaryotic Chromatin ◽  
Transcriptional Start Sites

The eukaryotic nucleosome is the fundamental unit of chromatin, comprising a protein octamer that wraps ∼147 bp of DNA and has essential roles in DNA compaction, replication and gene expression. Nucleosomes and chromatin have historically been considered to be unique to eukaryotes, yet studies of select archaea have identified homologs of histone proteins that assemble into tetrameric nucleosomes. Here we report the first archaeal genome-wide nucleosome occupancy map, as observed in the halophile Haloferax volcanii. Nucleosome occupancy was compared with gene expression by compiling a comprehensive transcriptome of Hfx. volcanii. We found that archaeal transcripts possess hallmarks of eukaryotic chromatin structure: nucleosome-depleted regions at transcriptional start sites and conserved −1 and +1 promoter nucleosomes. Our observations demonstrate that histones and chromatin architecture evolved before the divergence of Archaea and Eukarya, suggesting that the fundamental role of chromatin in the regulation of gene expression is ancient.

scholarly journals CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Martin Franke ◽  
Elisa De la Calle-Mustienes ◽  
Ana Neto ◽  
María Almuedo-Castillo ◽  
Ibai Irastorza-Azcarate ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Chromatin Structure ◽  
Zebrafish Model ◽  
Developmental Gene Expression ◽  
Chromatin Interactions ◽  
Fundamental Requirement ◽  
Regulatory Landscapes

AbstractCoordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes.

scholarly journals The Role of Id2 in the Regulation of Chromatin Structure and Gene Expression

10.5772/54969 ◽  
2013 ◽  
Author(s):  
Elena R. ◽  
Luis Torres ◽  
Rosa Zaragoza ◽  
Juan R.
Keyword(s):  
Gene Expression ◽  
Chromatin Structure

Chromosomal Loop Editing Reveals New Epigenomic Landscape in the β-Globin Locus with Implications for Hemoglobinopathy Therapies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 813-813
Author(s):  
Pamela Himadewi ◽  
Xiaotian Zhang ◽  
Haley Gore ◽  
Xue Qing David Wang
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Gene Editing ◽  
Fetal Hemoglobin ◽  
Fold Increase ◽  
Chromatin Loop ◽  
Erythroid Progenitors ◽  
Hemoglobin Gene ◽  
Ctcf Site

Human β-globin locus consists of at least six genes encoding components of the oxygen transport protein hemoglobin and an upstream locus control region (LCR) containing five DNase I hypersensitive sites. In addition, there are at least four conserved CTCF insulator elements surrounding the locus, which form dynamic chromatin interaction patterns across different cell types in the course of hematopoietic stem and progenitor cells (HSPCs) development. Chromatin conformation of the β-globin locus in normal adult CD34+ HSPCs reveals the formation of three topological associated domains (TADs), in which individual TAD boundaries are demarcated by CTCF sites (Figure 1). By comparing chromatin loop interactions between CD34+ HSPCs and its differentiated erythroid progenitors, we identify a chromatin loop that forms in erythroid progenitors and is not evident in the CD34+ HSPCs. Detailed examination of this loop shows that a DNase I hypersensitivity site, also called 3'HS1, overlaps with a CTCF site that forms a loop with another CTCF site adjacent to OR52A5 gene (Figure 2). To investigate the role of this specific chromatin loop in the regulation of hemoglobin gene expression, we knock out the 3'HS1 CTCF motif in adult CD34+ HSPCs under erythroid differentiation medium by CRISPR/Cas9-mediated gene editing. We find that deletion of 3'HS1 CTCF results in a 2-fold decrease of β-globin (HBB) and a 4-fold increase of the fetal hemoglobin gene encoded by γ-globin (HBG1/2) in erythroid colonies of edited CD34+ cells (Figure 3). Elevation of fetal hemoglobin upon 3'HS1 CTCF deletion was also confirmed in human umbilical cord blood-derived erythroid progenitor-2 cells (HUDEP-2), which results in a 12-fold increase of γ-globin expression (Figure 4). These results suggest that the 3'HS1 CTCF plays a crucial role in regulating the expression of fetal hemoglobin gene, however it remains unclear whether changes in chromatin structure is responsible for these changes. CTCF looping interactions have been described to form under convergent directionality. To validate the role of 3'HS1 CTCF in establishing chromatin interactions at the β-globin locus, we aim to invert this binding motif and evaluate how it disrupts chromatin organization and gene expression at this locus. Deciphering the underlying mechanisms will shed light on how three-dimensional chromatin structure is reorganized in differentiating erythroid cells as it undergoes nuclear condensation. Furthermore, elevation of fetal hemoglobin expression can potentially be a new therapeutic gene editing strategy to treat sickle cell disease and some cases of β-hemoglobinopathies. Disclosures No relevant conflicts of interest to declare.

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