it is tempting to speculate that these NF-kB signaling-dependent targets may play a role in TEL-JAK2-induced leukemogenesis

May 25, 2017

revealed that the local chromatin organization is one of the major players in the in vivo regulation of globin genes expression. There are 5 developmentally specific genes including embryonic, fetal, and adult globins in the human b-globin gene cluster on chromosome 11. The locus control region of b-globin gene cluster, containing 5 DNase I-hypersensitive sites, locates in the far upstream region of the cluster and is able to enhance tissuespecific b-globin genes expression. In the b-globin locus, the actively expressing globin genes are in close proximity to LCR to form a specialized structure that was termed as ACH. However, this higher order chromatin structure is not directly associated with gene transcription. Erythroid-specific transacting factors, such as EKLF, GATA-1, and FOG are indispensable factors to recruit the active b-like globin genes to the ACH. The details of how this ACH structure was established and maintained are still unclear. There are many candidate MARs in the b-globin cluster appear to be important in regulating the b-like globin genes expression. MARs flanking the e- or c-globin genes or within the b-globin second intervening sequence have been proposed as regulatory elements for globin genes expression or hemoglobin switching. But how these MAR elements regulate the gene expression is only addressed most recently. SATB1 was found to be present in the erythroid cells and the binding of SATB1 to some MARs can up-regulate the expression of e-globin gene. These studies indicate that SATB1 could mediate the function of MAR elements in directing the expression of b-globin genes. MAR Elements & Gene Expression In this report, we identified a new MAR element within the bglobin locus and observed the SATB1 mediated inter-MAR association by applying several approaches. We also demonstrated that the inter-MAR association plays an important role in regulating the expression of b-like globin genes possibly ASA-404 chemical information through influencing the establishment of the ACH. In light of the global regulatory role of SATB1, our data suggest that SATB1 is possibly an important regulator of early erythroid differentiation by influencing the chromatin organization. Results The identification of a new MAR element in the b-globin cluster We applied an improved method QACT to search the spatially associated chromatin fragments with a previously identified MAR element, which locate upstream of HS2 in K562 cells. The method is based on the recently reported ACT method and could quantitatively identify previously unknown chromatin fragments associated with a given chromatin fragment. The MARHS2 is a well known MAR element that had been proved to regulate the b-like globin genes expression. There were 11911275 totally 3 restriction fragments identified by QACT assay that show obvious association with the MARHS2. The fragments from the 59-flanking region of e-globin gene promoter and 39 -flanking region of cA -globin gene contain the supposed potential MARs that have already been reported. Another restriction fragment that showed high association frequency with MARHS2 locates at the interval region between HS4 and HS5. This newly identified fragment showed high MAR potential when analyzed with MARwiz . The nuclear extraction/DNA retention assay that is used to prove the enrichment of this fragment in NM associating chromatin also confirmed the high MAR possibility of 19187978 this fragment. SATB1 specifically binds to double stranded BUR sequences by recognizing a speci