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Promoter-proximal transcription factor binding is transcriptionally active when coupled with nucleosome repositioning in immediate vicinity.

Yadav VK, Thakur RK, Eckloff B, Baral A, Singh A, Halder R, Kumar A, Alam MP, Kundu TK, Pandita R, Pandita TK, Wieben ED, Chowdhury S - Nucleic Acids Res. (2014)

Bottom Line: These suggest that the three aspects are genetically connected but the cause and effect relationships are still unknown.For example, physiologic TF binding studies involve many TFs, consequently, it is difficult to assign nucleosome reorganization to the binding site occupancy of any particular TF.Therefore, several aspects remain unclear: does TF binding influence nucleosome (re)organizations locally or impact the chromatin landscape at a more global level; are all or only a fraction of TF binding a result of reorganization in nucleosome occupancy and do all TF binding and associated changes in nucleosome occupancy result in altered gene expression?

View Article: PubMed Central - PubMed

Affiliation: GNR Center for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India.

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Nucleosome positions detected in A549 cells before and after inducing NME2. (A) UCSC browser representation of nucleosome positions with corresponding probe intensity at two loci on chromosome 12. (B) Nucleosome occupancy around TSS and expression level of corresponding genes in cells before (left panels) and after NME2 induction (right panels); gene expression was normalized within respective cases by z-transformation with respect to the mean expression level of the data sets. (C) Frequency of occurrence and location of nucleosomes around TSS. −1, +1, +2, +3, +4 denote sequential presence of nucleosomes with respect to their occurrence from TSS; percentage of total number of nucleosomes found in respective cases, before or after induction of NME2. (D) Left panel: distribution of repositioned nucleosomes around TSSs in NME2-induced cells relative to the status in cells before NME2 was induced; number of repositioned nucleosomes in a window size of 100 bp is shown on top. Right panel: expression of corresponding genes shown in triplicate before and after NME2 induction.
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Figure 2: Nucleosome positions detected in A549 cells before and after inducing NME2. (A) UCSC browser representation of nucleosome positions with corresponding probe intensity at two loci on chromosome 12. (B) Nucleosome occupancy around TSS and expression level of corresponding genes in cells before (left panels) and after NME2 induction (right panels); gene expression was normalized within respective cases by z-transformation with respect to the mean expression level of the data sets. (C) Frequency of occurrence and location of nucleosomes around TSS. −1, +1, +2, +3, +4 denote sequential presence of nucleosomes with respect to their occurrence from TSS; percentage of total number of nucleosomes found in respective cases, before or after induction of NME2. (D) Left panel: distribution of repositioned nucleosomes around TSSs in NME2-induced cells relative to the status in cells before NME2 was induced; number of repositioned nucleosomes in a window size of 100 bp is shown on top. Right panel: expression of corresponding genes shown in triplicate before and after NME2 induction.

Mentions: We next asked whether altered state of chromatin in regulatory regions influenced NME2 occupancy and consequent gene expression changes. To test this, nucleosome positions were determined in the A549 cells before and after NME2 induction. Mono-nucleosomes were isolated by MNase digestion and we mapped nucleosome positions to putative promoter regions (−7.5 kb to 2.5 kb of TSSs) using tiled microarrays (Figure 2A) and found 157 634 and 162 570 nucleosomes before and after NME2 induction, respectively. Next, we checked the relationship between overall number of nucleosomes on each promoter and the expression level of corresponding gene and found that enriched promoter-nucleosome occupancy correlated with decreased expression of corresponding genes (r = −0.73; P < 0.05 before NME2 induction and r = −0.80; P < 0.05 after NME2 induction, Pearson correlation; Figure 2B).


Promoter-proximal transcription factor binding is transcriptionally active when coupled with nucleosome repositioning in immediate vicinity.

Yadav VK, Thakur RK, Eckloff B, Baral A, Singh A, Halder R, Kumar A, Alam MP, Kundu TK, Pandita R, Pandita TK, Wieben ED, Chowdhury S - Nucleic Acids Res. (2014)

Nucleosome positions detected in A549 cells before and after inducing NME2. (A) UCSC browser representation of nucleosome positions with corresponding probe intensity at two loci on chromosome 12. (B) Nucleosome occupancy around TSS and expression level of corresponding genes in cells before (left panels) and after NME2 induction (right panels); gene expression was normalized within respective cases by z-transformation with respect to the mean expression level of the data sets. (C) Frequency of occurrence and location of nucleosomes around TSS. −1, +1, +2, +3, +4 denote sequential presence of nucleosomes with respect to their occurrence from TSS; percentage of total number of nucleosomes found in respective cases, before or after induction of NME2. (D) Left panel: distribution of repositioned nucleosomes around TSSs in NME2-induced cells relative to the status in cells before NME2 was induced; number of repositioned nucleosomes in a window size of 100 bp is shown on top. Right panel: expression of corresponding genes shown in triplicate before and after NME2 induction.
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Related In: Results  -  Collection

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Figure 2: Nucleosome positions detected in A549 cells before and after inducing NME2. (A) UCSC browser representation of nucleosome positions with corresponding probe intensity at two loci on chromosome 12. (B) Nucleosome occupancy around TSS and expression level of corresponding genes in cells before (left panels) and after NME2 induction (right panels); gene expression was normalized within respective cases by z-transformation with respect to the mean expression level of the data sets. (C) Frequency of occurrence and location of nucleosomes around TSS. −1, +1, +2, +3, +4 denote sequential presence of nucleosomes with respect to their occurrence from TSS; percentage of total number of nucleosomes found in respective cases, before or after induction of NME2. (D) Left panel: distribution of repositioned nucleosomes around TSSs in NME2-induced cells relative to the status in cells before NME2 was induced; number of repositioned nucleosomes in a window size of 100 bp is shown on top. Right panel: expression of corresponding genes shown in triplicate before and after NME2 induction.
Mentions: We next asked whether altered state of chromatin in regulatory regions influenced NME2 occupancy and consequent gene expression changes. To test this, nucleosome positions were determined in the A549 cells before and after NME2 induction. Mono-nucleosomes were isolated by MNase digestion and we mapped nucleosome positions to putative promoter regions (−7.5 kb to 2.5 kb of TSSs) using tiled microarrays (Figure 2A) and found 157 634 and 162 570 nucleosomes before and after NME2 induction, respectively. Next, we checked the relationship between overall number of nucleosomes on each promoter and the expression level of corresponding gene and found that enriched promoter-nucleosome occupancy correlated with decreased expression of corresponding genes (r = −0.73; P < 0.05 before NME2 induction and r = −0.80; P < 0.05 after NME2 induction, Pearson correlation; Figure 2B).

Bottom Line: These suggest that the three aspects are genetically connected but the cause and effect relationships are still unknown.For example, physiologic TF binding studies involve many TFs, consequently, it is difficult to assign nucleosome reorganization to the binding site occupancy of any particular TF.Therefore, several aspects remain unclear: does TF binding influence nucleosome (re)organizations locally or impact the chromatin landscape at a more global level; are all or only a fraction of TF binding a result of reorganization in nucleosome occupancy and do all TF binding and associated changes in nucleosome occupancy result in altered gene expression?

View Article: PubMed Central - PubMed

Affiliation: GNR Center for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India.

Show MeSH