Chromatin Structure and Gene Expression

Conklin, Kathleen F.; Groudine, Mark

doi:10.1007/978-1-4613-8519-6_15

Cited by 30 publications

(16 citation statements)

References 289 publications

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“…Chromatin hypersensitivity to endonuclease digestion is a characteristic property of regulatory sequences in eucaryotic genes (6,50). The data presented in Fig.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, the 5' boundary of the sensitive region extends at least to the EcoRI site (650 base pairs from MspI site 8). This minimal length of the Pgk nuclease-sensitive region is somewhat larger than those in other active genes, which are usually about 200 to 500 base pairs long (6,50). The use of other restriction enzymes for nuclear digestion should help to map the boundaries more precisely.…”

Section: Discussionmentioning

confidence: 99%

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Demethylation of specific sites in the 5' region of the inactive X-linked human phosphoglycerate kinase gene correlates with the appearance of nuclease sensitivity and gene expression.

Hansen¹,

Ellis²,

Gartler³

1988

Mol. Cell. Biol.

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X8/6T2, a hamster-human hybrid cell line which contains an inactive human X chromosome, was treated with 5-azacytidine and selected for derepression of hypoxanthine-guanine phosphoribosyltransferase. Clones were examined for coreactivation of the phosphoglycerate kinase gene (Pgk). Of 68 of these hybrids, approximately 20% expressed measurable human phosphoglycerate kinase (PGK) activity. A 600-base-pair region of the Pgk 5' CpG cluster was examined for the methylation status of eight CCGG sites (site 1 being 5'-most) in a number of PGK-negative and PGK-positive cell lines. The inactive X chromosome is normally methylated at all eight sites, and this was also true for the majority of X8/6T2 cells. However, several PGK-negative hybrids were demethylated in the site 3 to site 6 region. PGK activity correlated with demethylation at both sites 6 and 7. The data for PGK-positive and -negative hybrids indicate that demethylation at or near site 7 was necessary for reactivation of Pgk. Chromatin sensitivity to MspI digestion in the nuclei of male lymphoblastoid cells and several PGK-positive and PGK-negative hybrids was examined. PGK-positive cell lines were hypersensitive to digestion, while PGK-negative hybrids were resistant. Cleavage at sites 6 and 7 was observed in all PGK-positive cell lines at each MspI concentration examined. Sites 7 and 8 were less accessible to digestion than site 6. Cleavage in the site 2 to site 5 region was observable at the lowest MspI concentration. In most PGK-positive hybrids, a nonspecific endogenous nuclease detected the presence of a hypersensitive region spanning at least 450 base pairs, bounded at the 3' end near HpaIl site 6. Nuclease hypersensitivity appears to be related to promoter activity, because sites 7 and 8 are in transcribed regions of the gene. These data indicate that specific sites within the CpG cluster have a dominant controlling influence over the Pgk promoter conformation and the transcriptional activation of Pgk.

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“…Chromatin hypersensitivity to endonuclease digestion is a characteristic property of regulatory sequences in eucaryotic genes (6,50). The data presented in Fig.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Demethylation of specific sites in the 5' region of the inactive X-linked human phosphoglycerate kinase gene correlates with the appearance of nuclease sensitivity and gene expression.

Hansen¹,

Ellis²,

Gartler³

1988

Mol. Cell. Biol.

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“…Increasing digestion is from left to right. 10 kb and a single subband of 1.4 + 0.15 kb. We analyzed the DNA sequence of the hypersensitive site region (kindly provided by E. A. Feingold and B.…”

mentioning

confidence: 99%

“…These hypersensitive sites are not present in adult bone marrow erythroid cells, in which the genes are transcriptionally silent (18) despite retaining DNase I sensitivity (2). The notion that chromatin structure may be important in the regulation of gene expression has been reviewed extensively (10,44).…”

mentioning

confidence: 99%

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Translocation of an erythroid-specific hypersensitive site in deletion-type hereditary persistence of fetal hemoglobin.

Elder¹,

Forrester²,

Thompson³

et al. 1990

Mol. Cell. Biol.

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Hereditary persistence of fetal hemoglobin (HPFH) can involve large deletions which eliminate the 3' end of the ,8-like globin gene cluster and more than 70 kilobases (kb) of flanking DNA. Blot hybridization revealed a DNase I-hypersensitive site extending from 1.1 to 1.4 kb downstream of the HPFH-1 3' deletion endpoint. The site was found in normal fetal and adult nucleated erythroid cells and in two erythroleukemia cell lines but not in nonerythroid cells and tissues. Simian virus 40 core enhancer-like sequences were found nonrandomly distributed within the boundaries of the site, which is contained in a fragment of known enhancer activity (E. A. Feingold and B. G. Forget, Blood, in press). A second hypersensitive site was found 0.5 kb upstream of the HPFH-1 3' deletion endpoint but was not erythroid specific. A third site, most prominent in fetal liver-derived erythroid cells, was found 1 kb upstream of the HPFH-2 deletion endpoint. As predicted by the locations of the deletion endpoints, the first two sites were translocated to within 12 kb of the A_Y gene in erythroid colonies derived from an HPFH-2 heterozygote and in hybrid mouse-human erythroid cells carrying the HPFH-2 deletion chromosome. Further analysis of this region showed that it was DNase I sensitive in erythroid and myeloid cells, indicating that it resides in an open chromatin domain. These observations suggest that alterations of chromatin structure flanking the fetal globin genes may contribute to abnormal gene regulation in deletion-type HPFH.

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Epigenetic Control of Gene Expression

Razin

Shemer

1999

Results and Problems in Cell Differentiation

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Chromatin Structure and Gene Expression

Cited by 30 publications

References 289 publications

Demethylation of specific sites in the 5' region of the inactive X-linked human phosphoglycerate kinase gene correlates with the appearance of nuclease sensitivity and gene expression.

Demethylation of specific sites in the 5' region of the inactive X-linked human phosphoglycerate kinase gene correlates with the appearance of nuclease sensitivity and gene expression.

Translocation of an erythroid-specific hypersensitive site in deletion-type hereditary persistence of fetal hemoglobin.

Epigenetic Control of Gene Expression

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