Article paragraph Question and binding site methylation specifically within acut

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Question and binding site methylation specifically within acute promyelocytic a leukaemia cells (NBH),andboth interact with P (PML bodies a sub-nudear structure disrupted in PML cells. The anomalous behaviour of these two transcription factors with respect to chromatin structure and DNA methylation may thus be related to a specialized mechanism seen only in pathologically altered cells. A map of distal DHS-to-promoter connections From examination of DNasel profiles across many cell types. observed that many known cell-selective enhancers become DHSs synchronously with the appearance of hypersensitivity at the pro- moter of their target gene (Supplementary 13). Togeneralizethis. we analysed the patterning of 1454,901 distal DHS (DHSs separated from a TSS by at least one other DHS across 79 diverse cell types Distal DHSs conneenad Promoter DHSe connected supplementary Methods and Sopplementary Table 6), and corre- per Promoter DHS per distal DHS lated the cross-cell type DNase signal at each DHS position with that at all promoters within t 500 kb (Supplementary Pig, 14a. We identified a total of 578905 DHss that were highly correlated (r 02) 1-10 11-2008N with at least one promoter (P

Explanation / Answer

DHSs are sites in chromatin which exposes the DNA to the enzyme DNase.

Promoters, enhancers, silencers, insulators are cis regulatory elements. They aid in the regulation of transcription by allowing the binding of transcription factors.

The chromatin structure is made of nucleosome (bunch of histone proteins) around which the DNA is spun. These nucleosome supercoils to form chromatin. It compacts the DNA so that it can fit in the nucleus. Transcription occurs during the interphase of mitosis. During transcription, the compact nature of the chromatin is loosened. The cis regulatory elements are the first to exposed in transcription. In this stage the cis elements are in less condensed state which exposes more DNA to the enzyme DNase. It is because these elements do not have the nucleosome. When these elements are dissolved by DNase, then the transcription factors are not bound and hence the initiation stops.

Hence the DHSs are used to map the cis regulatory elements which serves as a marker for various studies.

Note: DNase 1 is an ending lease which cleaves the phosphodiester backbone of DNA.

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