The 5′-flanking cis-acting elements of the human ɛ-globin gene associates with the nuclear matrix and binds to the nuclear matrix proteins

Yan, Zhi; Qian, Ruo Lan

doi:10.1038/cr.1998.21

Cited by 4 publications

(7 citation statements)

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“…We applied an improved method QACT (quantitative associated chromatin trap) to search the spatially associated chromatin fragments with a previously identified MAR element, which locate upstream of HS2 (MAR HS2 ) in K562 cells [29], [30]. The method is based on the recently reported ACT method [12] and could quantitatively identify previously unknown chromatin fragments associated with a given chromatin fragment [31].…”

Section: Resultsmentioning

confidence: 99%

Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

Wang

et al. 2009

PLoS ONE

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Matrix attachment regions (MARs) are important in chromatin organization and gene regulation. Although it is known that there are a number of MAR elements in the β-globin gene cluster, it is unclear that how these MAR elements are involved in regulating β-globin genes expression. Here, we report the identification of a new MAR element at the LCR(locus control region) of human β-globin gene cluster and the detection of the inter-MAR association within the β-globin gene cluster. Also, we demonstrate that SATB1, a protein factor that has been implicated in the formation of network like higher order chromatin structures at some gene loci, takes part in β-globin specific inter-MAR association through binding the specific MARs. Knocking down of SATB1 obviously reduces the binding of SATB1 to the MARs and diminishes the frequency of the inter-MAR association. As a result, the ACH establishment and the α-like globin genes and β-like globin genes expressions are affected either. In summary, our results suggest that SATB1 is a regulatory factor of hemoglobin genes, especially the early differentiation genes at least through affecting the higher order chromatin structure.

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Section: Resultsmentioning

confidence: 99%

Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

Wang

et al. 2009

PLoS ONE

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“…13 Using the potential MAR at the 5Ј region of HS2 (HS2-M1, CATTATAATTA-ACTGTTATTTTTTA, located 158 bp upstream of HindIII in the HS2 core) as a DNA probe for EMSA, we observed a slow migrating band from the K562 nuclear extract ( Figure 3B, lanes 1-4). This band was competed by the SATB1-binding sequence Wt (25) 7 ) (S), 17 and by SATB1 antibody (␣S), but not by a mutated SATB1-binding competitor (⌬S), mut (24) 8 (5Ј-(TCTTTAATTTC-TACTGCTTTAGAA) 8 -3Ј).…”

Section: Satb1 Interacts With Mars Localized In the ␤-Globin Cluster mentioning

confidence: 99%

“…[12][13][14][15]42 It has been suggested that SATB1 may participate in a dynamic process to mediate looping of the ␤-globin locus to achieve transcriptional control, advancing the notion that SATB1 binding to MARs may facilitate the remodeling of local chromatin structure and may bring distal regulatory elements in close proximity to promoters. 16 We screened these potential MARs or SATB1-binding regions [12][13][14][15]42 and found that SATB1 bound in vivo to HS2 (M1) and the ⑀-globin promoter M ⑀ , but did not bind to previously reported in vitro binding sites in the 3Ј ␥-globin enhancer or ␤-IVS2 or to ATC sequence-rich regions in HS3, HS4, or the 5Ј region of the ␥-or ␤-globin genes. HS2 was the first hypersensitive site identified in the LCR with erythroid-specific developmental stage-independent enhancer activity 43 and HS2, but not HS3 or HS4, activates transcription of the ⑀-globin gene in K562 cells in studies using chromatinized episomes.…”

Section: Human Primary Erythroid Progenitor Cellsmentioning

confidence: 99%

“…10,11 MARs found flanking the ⑀-or ␥-globin genes or within the ␤-globin second intervening sequence (IVS2) have been proposed as regulatory elements for specific globin gene expression or hemoglobin switching. [12][13][14][15][16] Special AT-rich binding protein 1 (SATB1) binds to doublestranded BUR sequences, specifically recognizing a specialized DNA context (an ATC sequence context), characterized by a cluster of sequence stretches with well-mixed As and Ts but either Cs or Gs exclusively on one strand (designated as ATC sequences). 17 SATB1 has roles in tissue-specific organization of DNA sequences, in regulation of gene expression by acting as a "landing platform" for chromatin-remodeling enzymes and in designation of the region-specific histone modification in vivo.…”

Section: Introductionmentioning

confidence: 99%

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SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression

Wen

Huang

Rogers

et al. 2005

Blood

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Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. Here we show SATB1 family protein induction during early human adult erythroid progenitor cell differentiation concomitant with ⑀-globin expression. Erythroid differentiation of human erythroleukemia K562 cells by hemin simultaneously increases ␥-globin and down-regulates SATB1 family protein and ⑀-globin gene expression. Chromatin immunoprecipitation using anti-SATB1 antibody shows selective binding in vivo in the ␤-globin cluster to the hypersensitive site 2 (HS2) in the locus control region (LCR) and to the ⑀-globin promoter. SATB1 overexpression increases ⑀-globin and decreases ␥-globin gene expression accompanied by histone hyperacetylation and hypomethylation in chromatin from the ⑀-globin promoter and HS2, and histone hypoacetylation and hypermethylation associated with the ␥-globin promoter. In K562 cells SATB1 family protein forms a complex with CREB-binding protein ( IntroductionThe human ␤-globin gene cluster on chromosome 11 consists of 5 developmentally specific genes for embryonic (⑀), fetal ( G ␥, A ␥), and adult (␦, ␤) globins. A strong enhancer, located in the far upstream region of the cluster called the locus control region (LCR), contains 5 DNase I hypersensitive (HS) sites and is able to enhance tissue-specific globin gene expression and provide a high level of transcription activity from human globin gene constructs in transgenic mice. Transcription factors such as erythroid Krüppel-like factor (EKLF), GATA-1, and NF-E2, that bind to the LCR and other regulatory elements, and promoters in the globin gene locus, have been reported to regulate chromatin histone acetylation by associating with histone acetyltransferases. [1][2][3] The LCR is required to increase the rate of transcription but may be dispensable for formation of an open chromatin domain of a downstream active globin gene in erythroid cells. 4,5 For globin gene expression, spatial organization of the ␤-globin cluster requires special interactions between distal transcriptional elements in the LCR and downstream active globin genes. Some developmental specificity between individual hypersensitive sites in the LCR and downstream globin genes is evident such as the interaction between HS2 and ⑀-globin for transcription activation. 6 Complex packaging of eukaryotic chromosomes in nuclei creates chromatin loops and matrix/scaffold attachment regions (MARs/SARs; the term MARs is used here), originally identified as gDNA fragments that remain tightly associated with saltextracted and DNase I-digested nuclei, have been postulated to be localized at the base of chromatin loops. 7 MARs identified by such criteria often contain a base-unpairing region (BUR), the DNA bases of which become continuously unpaired when subjected to negative superhelical strain. 8,9 Many candidate MARs in the ␤-globin cluster appear to be in regions of mass binding sites for transcription ...

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“…These elements are not identical but have a number of common properties: they are usually about 1,000 bp or slightly more, are AT-rich, they often form non-canonical DNA structures (palindromes or different distortions of the double helix), are often situated near cisregulatory sequences (enhancers, promotors, insulators, and transcription factor binding sequences) and contain sites or regions hypersensitive to DNAse I. Moreover, MARs are enriched in topoisomerase II cleavage sites [Gasser and Laemmli, 1986;Boulikas, 1993Boulikas, , 1994Bode et al, 1995;Yan and Qian, 1998;Porter et al, 1999;Razin, 2001;Holmes-Davis and Comai, 2002;Felsenfeld et al, 2004;Yusufzai and Felsenfeld, 2004].…”

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confidence: 98%

Inhibition of DNA topoisomerase II may trigger illegitimate recombination in living cells: Experiments with a model system

Umanskaya

Lebedeva

Гаврилов

et al. 2006

J of Cellular Biochemistry

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We have developed a plasmid test system to study recombination in vitro and in mammalian cells in vivo, and to analyze the possible role of DNA topoisomerase II. The system is based on a plasmid construct containing an inducible marker gene ccdB ("killer" (KIL) gene) whose product is lethal for bacterial cells, flanked by two different potentially recombinogenic elements. The plasmids were subjected to recombinogenic conditions in vitro or in vivo after transient transfection into COS-1 cells, and subsequently transformed into E. coli which was then grown in the presence of the ccdB gene inducer. Hence, all viable colonies contained recombinant plasmids since only recombination between the flanking regions could remove the KIL gene. Thus, it was possible to detect recombination events and to estimate their frequency. We found that the frequency of topoisomerase II-mediated recombination in vivo is significantly higher than in a minimal in vitro system. The presence of VM-26, an inhibitor of the religation step of the topoisomerase II reaction, increased the recombination frequency by 60%. We propose that cleavable complexes of topoisomerase II are either not religated, triggering error-prone repair of the DNA breaks, or are incorrectly religated resulting in strand exchange. We also studied the influence of sequences known to contain preferential breakpoints for recombination in vivo after chemotherapy with topoisomerase II-targeting drugs, but no preferential stimulation of recombination by these sequences was detected in this non-chromosomal context.

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The 5′-flanking cis-acting elements of the human ɛ-globin gene associates with the nuclear matrix and binds to the nuclear matrix proteins

Cited by 4 publications

References 23 publications

Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression

Inhibition of DNA topoisomerase II may trigger illegitimate recombination in living cells: Experiments with a model system

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