Extinction of phosphoenolpyruvate carboxykinase gene expression is associated with loss of a specific chromatin-binding protein from a far upstream domain

1990 ◽  
Vol 10 (7) ◽  
pp. 3782-3787
Author(s):  
Y T Ip ◽  
R E Fournier ◽  
R Chalkley
Keyword(s):  
Chromatin Structure ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Specific Protein ◽  
Gene Activity ◽  
Upstream Region ◽  
Hypersensitive Site ◽  
Chromosome 11 ◽  
Protein Factor ◽  
Hypersensitive Sites ◽  
Liver Gene

We have analyzed the chromatin structure of the phosphoenolpyruvate carboxykinase (PEPCK) gene in hepatoma x fibroblast hybrids with different extinction phenotypes. These hybrids included a karyotypically complete hybrid in which all liver gene activity was extinguished, a microcell hybrid that contained a single mouse chromosome 11 and in which PEPCK gene activity was decreased but inducible by cyclic AMP, and a segregant line that had lost all mouse chromosomes and in which the PEPCK gene was reexpressed. We found that only in the completely extinguished hybrid was PEPCK chromatin structure radically different from that in the parental hepatoma cells. In this hybrid, there was no evidence of any factors binding to the promoter or to the upstream hypersensitive site at -4800 base pairs. In the other cell lines, even when PEPCK gene transcription was low, the PEPCK chromatin showed characteristic structures typical of a transcriptionally competent gene, with hypersensitive sites at positions previously described. Loss of the upstream hypersensitive site was also shown to be correlated with the absence of a liver-specific protein factor that binds specifically to the upstream region.

scholarly journals Extinction of phosphoenolpyruvate carboxykinase gene expression is associated with loss of a specific chromatin-binding protein from a far upstream domain.

1990 ◽  
Vol 10 (7) ◽  
pp. 3782-3787 ◽  
Author(s):  
Y T Ip ◽  
R E Fournier ◽  
R Chalkley
Keyword(s):  
Chromatin Structure ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Specific Protein ◽  
Gene Activity ◽  
Upstream Region ◽  
Hypersensitive Site ◽  
Chromosome 11 ◽  
Protein Factor ◽  
Hypersensitive Sites ◽  
Liver Gene

We have analyzed the chromatin structure of the phosphoenolpyruvate carboxykinase (PEPCK) gene in hepatoma x fibroblast hybrids with different extinction phenotypes. These hybrids included a karyotypically complete hybrid in which all liver gene activity was extinguished, a microcell hybrid that contained a single mouse chromosome 11 and in which PEPCK gene activity was decreased but inducible by cyclic AMP, and a segregant line that had lost all mouse chromosomes and in which the PEPCK gene was reexpressed. We found that only in the completely extinguished hybrid was PEPCK chromatin structure radically different from that in the parental hepatoma cells. In this hybrid, there was no evidence of any factors binding to the promoter or to the upstream hypersensitive site at -4800 base pairs. In the other cell lines, even when PEPCK gene transcription was low, the PEPCK chromatin showed characteristic structures typical of a transcriptionally competent gene, with hypersensitive sites at positions previously described. Loss of the upstream hypersensitive site was also shown to be correlated with the absence of a liver-specific protein factor that binds specifically to the upstream region.

scholarly journals Erythroid-specific nuclease-hypersensitive sites flanking the human beta-globin domain.

1990 ◽  
Vol 10 (8) ◽  
pp. 4324-4333 ◽  
Author(s):  
V Dhar ◽  
A Nandi ◽  
C L Schildkraut ◽  
A I Skoultchi
Keyword(s):  
Dna Sequences ◽  
Chromatin Structure ◽  
Globin Gene ◽  
Embryonal Carcinoma Cell ◽  
Globin Genes ◽  
Beta Globin ◽  
Hypersensitive Site ◽  
Specific Expression ◽  
Structure Changes ◽  
Hypersensitive Sites

Recent evidence suggests that DNA sequences from the region lying 5' of the human epsilon-globin gene are important for erythroid-specific expression of human beta-like globin genes. This region, as well as a region 20 kilobases (kb) downstream from the beta-globin gene, contains a set of developmentally stable, DNase I-superhypersensitive sites that are thought to reflect a chromatin structure supporting active globin gene expression. We have analyzed the chromatin structure in these two regions in a wide variety of nonerythroid and erythroid cells. The study included analysis of chromatin structure changes occurring during globin gene activation in mouse erythroleukemia-human nonerythroid cell hybrids. The results identified a hypersensitive site (III) 14.8 kb upstream of the epsilon-globin gene that was strictly correlated with active globin gene transcription. Interestingly, a multipotent human embryonal carcinoma cell line exhibited a hypersensitive site (IV) 18.4 kb upstream of epsilon-globin that was absent in all other nonerythroid cells examined, suggesting that chromatin structure changes at specific hypersensitive sites during embryonic development may also be important in globin gene repression.

scholarly journals NF-E2 disrupts chromatin structure at human beta-globin locus control region hypersensitive site 2 in vitro.

1996 ◽  
Vol 16 (10) ◽  
pp. 5634-5644 ◽  
Author(s):  
J A Armstrong ◽  
B M Emerson
Keyword(s):  
Control Region ◽  
Chromatin Structure ◽  
Locus Control Region ◽  
Dnase I ◽  
Hematopoietic Cell ◽  
Beta Globin ◽  
Hypersensitive Site ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites

The human beta-globin locus control region (LCR) is responsible for forming an active chromatin structure extending over the 100-kb locus, allowing expression of the beta-globin gene family. The LCR consists of four erythroid-cell-specific DNase I hypersensitive sites (HS1 to -4). DNase I hypersensitive sites are thought to represent nucleosome-free regions of DNA which are bound by trans-acting factors. Of the four hypersensitive sites only HS2 acts as a transcriptional enhancer. In this study, we examine the binding of an erythroid protein to its site within HS2 in chromatin in vitro. NF-E2 is a transcriptional activator consisting of two subunits, the hematopoietic cell-specific p45 and the ubiquitous DNA-binding subunit, p18. NF-E2 binds two tandem AP1-like sites in HS2 which form the core of its enhancer activity. In this study, we show that when bound to in vitro-reconstituted chromatin, NF-E2 forms a DNase I hypersensitive site at HS2 similar to the site observed in vivo. Moreover, NF-E2 binding in vitro results in a disruption of nucleosome structure which can be detected 200 bp away. Although NF-E2 can disrupt nucleosomes when added to preformed chromatin, the disruption is more pronounced when NF-E2 is added to DNA prior to chromatin assembly. Interestingly, the hematopoietic cell-specific subunit, p45, is necessary for binding to chromatin but not to naked DNA. Interaction of NF-E2 with its site in chromatin-reconstituted HS2 allows a second erythroid factor, GATA-1, to bind its nearby sites. Lastly, nucleosome disruption by NF-E2 is an ATP-dependent process, suggesting the involvement of energy-dependent nucleosome remodeling factors.

Erythroid-specific nuclease-hypersensitive sites flanking the human beta-globin domain

1990 ◽  
Vol 10 (8) ◽  
pp. 4324-4333
Author(s):  
V Dhar ◽  
A Nandi ◽  
C L Schildkraut ◽  
A I Skoultchi
Keyword(s):  
Dna Sequences ◽  
Chromatin Structure ◽  
Globin Gene ◽  
Embryonal Carcinoma Cell ◽  
Globin Genes ◽  
Beta Globin ◽  
Hypersensitive Site ◽  
Specific Expression ◽  
Structure Changes ◽  
Hypersensitive Sites

Recent evidence suggests that DNA sequences from the region lying 5' of the human epsilon-globin gene are important for erythroid-specific expression of human beta-like globin genes. This region, as well as a region 20 kilobases (kb) downstream from the beta-globin gene, contains a set of developmentally stable, DNase I-superhypersensitive sites that are thought to reflect a chromatin structure supporting active globin gene expression. We have analyzed the chromatin structure in these two regions in a wide variety of nonerythroid and erythroid cells. The study included analysis of chromatin structure changes occurring during globin gene activation in mouse erythroleukemia-human nonerythroid cell hybrids. The results identified a hypersensitive site (III) 14.8 kb upstream of the epsilon-globin gene that was strictly correlated with active globin gene transcription. Interestingly, a multipotent human embryonal carcinoma cell line exhibited a hypersensitive site (IV) 18.4 kb upstream of epsilon-globin that was absent in all other nonerythroid cells examined, suggesting that chromatin structure changes at specific hypersensitive sites during embryonic development may also be important in globin gene repression.

scholarly journals Genetic basis and identification of candidate genes for wooden breast and white striping in commercial broiler chickens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juniper A. Lake ◽  
Jack C. M. Dekkers ◽  
Behnam Abasht
Keyword(s):  
Candidate Genes ◽  
Broiler Chickens ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Specific Protein ◽  
Chromosome 11 ◽  
A Genome ◽  
White Striping ◽  
Commercial Broiler ◽  
Wooden Breast

AbstractWooden breast (WB) and white striping (WS) are highly prevalent and economically damaging muscle disorders of modern commercial broiler chickens characterized respectively by palpable firmness and fatty white striations running parallel to the muscle fiber. High feed efficiency and rapid growth, especially of the breast muscle, are believed to contribute to development of such muscle defects; however, their etiology remains poorly understood. To gain insight into the genetic basis of these myopathies, a genome-wide association study was conducted using a commercial crossbred broiler population (n = 1193). Heritability was estimated at 0.5 for WB and WS with high genetic correlation between them (0.88). GWAS revealed 28 quantitative trait loci (QTL) on five chromosomes for WB and 6 QTL on one chromosome for WS, with the majority of QTL for both myopathies located in a ~ 8 Mb region of chromosome 5. This region has highly conserved synteny with a portion of human chromosome 11 containing a cluster of imprinted genes associated with growth and metabolic disorders such as type 2 diabetes and Beckwith-Wiedemann syndrome. Candidate genes include potassium voltage-gated channel subfamily Q member 1 (KCNQ1), involved in insulin secretion and cardiac electrical activity, lymphocyte-specific protein 1 (LSP1), involved in inflammation and immune response.

The chromatin structure of Saccharomyces cerevisiae autonomously replicating sequences changes during the cell division cycle

1991 ◽  
Vol 11 (10) ◽  
pp. 5301-5311
Author(s):  
J A Brown ◽  
S G Holmes ◽  
M M Smith
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Division ◽  
Chromatin Structure ◽  
Dnase I ◽  
S Phase ◽  
Cell Division Cycle ◽  
Characteristic Change ◽  
The Core ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites

The chromatin structures of two well-characterized autonomously replicating sequence (ARS) elements were examined at their chromosomal sites during the cell division cycle in Saccharomyces cerevisiae. The H4 ARS is located near one of the duplicate nonallelic histone H4 genes, while ARS1 is present near the TRP1 gene. Cells blocked in G1 either by alpha-factor arrest or by nitrogen starvation had two DNase I-hypersensitive sites of about equal intensity in the ARS element. This pattern of DNase I-hypersensitive sites was altered in synchronous cultures allowed to proceed into S phase. In addition to a general increase in DNase I sensitivity around the core consensus sequence, the DNase I-hypersensitive site closest to the core consensus became more nuclease sensitive than the distal site. This change in chromatin structure was restricted to the ARS region and depended on replication since cdc7 cells blocked near the time of replication initiation did not undergo the transition. Subsequent release of arrested cdc7 cells restored entry into S phase and was accompanied by the characteristic change in ARS chromatin structure.

scholarly journals Formation of stable chromatin structures on the histone H4 gene during differentiation in Tetrahymena thermophila.

1986 ◽  
Vol 6 (8) ◽  
pp. 3014-3017 ◽  
Author(s):  
D S Pederson ◽  
K Shupe ◽  
G A Bannon ◽  
M A Gorovsky
Keyword(s):  
Chromatin Structure ◽  
Transcriptional Control ◽  
Tetrahymena Thermophila ◽  
Micrococcal Nuclease ◽  
Histone H4 ◽  
Hypersensitive Sites ◽  
Nuclear Differentiation ◽  
Histone Gene Transcription ◽  
The Relationship ◽  
I Gene

The relationship between chromatin structure and the transcriptional activity of the histone H4-I gene of Tetrahymena thermophila was explored. Indirect end-labeling studies demonstrated that major DNase I- and micrococcal nuclease-hypersensitive sites flank the active macronuclear genes but not the inactive micronuclear genes. Runon transcription experiments with isolated macronuclei indicated that histone gene transcription rates decreased when cells were starved. However, macronuclear nuclease-hypersensitive sites persisted upon starvation. Thus, one level of transcriptional control of the H4-I gene results in altered chromatin structure and is established during nuclear differentiation. The rate of transcription is also controlled, but not through hypersensitive site-associated structures.

scholarly journals Topoisomerase activity is linked to altered nucleosome positioning and transcriptional regulation in the fission yeast fbp1 gene

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242348
Author(s):  
Ryuta Asada ◽  
Satoshi Senmatsu ◽  
Ben Montpetit ◽  
Kouji Hirota
Keyword(s):  
Transcriptional Regulation ◽  
Fission Yeast ◽  
Chromatin Structure ◽  
Promoter Region ◽  
Nucleosome Positioning ◽  
Dna Topology ◽  
Upstream Region ◽  
Inactive Form ◽  
Topological State ◽  
Transcriptional Output

Chromatin structure, including nucleosome positioning, has a fundamental role in transcriptional regulation through influencing protein-DNA interactions. DNA topology is known to influence chromatin structure, and in doing so, can also alter transcription. However, detailed mechanism(s) linking transcriptional regulation events to chromatin structure that is regulated by changes in DNA topology remain to be well defined. Here we demonstrate that nucleosome positioning and transcriptional output from the fission yeast fbp1 and prp3 genes are altered by excess topoisomerase activity. Given that lncRNAs (long noncoding RNAs) are transcribed from the fbp1 upstream region and are important for fbp1 gene expression, we hypothesized that local changes in DNA topological state caused by topoisomerase activity could alter lncRNA and fbp1 transcription. In support of this, we found that topoisomerase overexpression caused destabilization of positioned nucleosomes within the fbp1 promoter region, which was accompanied by aberrant fbp1 transcription. Similarly, the direct recruitment of topoisomerase, but not a catalytically inactive form, to the promoter region of fbp1 caused local changes in nucleosome positioning that was also accompanied by altered fbp1 transcription. These data indicate that changes in DNA topological state induced by topoisomerase activity could lead to altered fbp1 transcription through modulating nucleosome positioning.

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