Chromatin Structure

The integrity of the long range chromosomal domain enveloping the c-myc gene appears to be necessary for correct control of c-myc transcription in vivo (Levens et al., 1997; Liu and Levens, 2006; Potter and Marcu, 1997). So, reconstructed c-myc genes, containing 50 kb of continuous DNA sequences including the promoter, the three exons and approximately 20 kb of each 5' and 3' flanking sequences, failed to recapitulate many, if not most, features of the normal c-myc transcriptional control (Lavenu et al., 1994; Mautner etal., 1996).

Chromatin remodeling provides an additional level for control of the c-myc promoter. Several components of the mammalian ATP-dependent SWI/SNF nucleosome remodeling complexes BAF and PBAF, for example their ATPase subunit BRG-1 (Brahma-related gene-1), were found to be associated with the c-myc promoter indicating their implication in control of c-myc transcription. In addition, several transcription factors were reported to recruit different HAT and HDAC complexes to the c-myc promoter and to influence its histone acetylation status. Also association of several subunits of a MLL/SET1-type HMT (histone methyltransferase) complex, for example, of the HMT MLL2, with the c-myc promoter has been described suggesting its involvement in regulation of c-myc transcription. Regulation of c-myc transcription by chromatin remodeling is complex and not completely understood.

Mapping of nucleosomes on active c-myc genes in proliferating undiffer-entiated promyelocytic HL-60 leukemia cells and on inactive c-myc genes in DMSO-treated differentiated HL-60 cells revealed that the nucleosomes 3 (upstream region), 9 (P0 promoter region), 12 (directly upstream of P1 promoter), and 13 (at P1 promoter) were present only on the inactive c-myc genes (Fig. 3A; Pullner et al., 1996). In contrast, the P2 promoter was never found to be occupied by a nucleosome (Albert et al., 1997; Michelotti et al., 1996b; Pullner et al., 1996). This difference between the promoters P1 and P2 points to different modes of their repression during DMSO-induced HL-60 cell differentiation. Like the absence of the nucleosomes, the presence of the corresponding DNAse I-hypersensitive sites II2 (P0 promoter region), III1 and III2 (P1 promoter region) correlated with the activity of the c-myc

A Nucleosomal structure of active and inactive c-myc genes

P0 P1

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