organize the E. coli chromosome? According to the current view, SMC complexes organize chromosomes by extruding DNA loops. SMC complexes translocate along DNA to extrude loops in a cis-manner (on the same DNA molecule), wherein the size of loops depends on processivity of the complex. SMC complexes from different organisms differ in the mechanism of loop extrusion. Single molecule fluorescence microscopy of MukBEF in E. coli suggests that the minimum functional unit in vivo is a dimer of dimers. This unit is formed by joining of two ATP-bound MukBEF complexes through MukF-mediated dimerization. MukBEF localizes in the cell as 1-3 clusters that are elongated parallel to the long axis of the cell. Each cluster contains an average ~ 8-10 dimers of dimers. According to the current model, the MukBEF extrudes DNA loops in a “rock-climbing” manner. A dimer of the dimers releases one segment of DNA and capture a new DNA segment without dissociating from the chromosome. Besides DNA looping, a link between negative supercoiling and in vivo MukBEF function together with the ability of the MukB subunit to constrain negative supercoils in vitro suggests that MukBEF organizes DNA by generating supercoils. Role of NAPs and naRNAs In addition to contributing to the chromosome compaction by bending, bridging, and looping DNA at a smaller scale (~1-kb), NAPs participate in DNA condensation and organization by promoting long-rang DNA-DNA contacts. Two NAPs, Fis and HU, emerged as the key players in promoting long-range DNA-DNA contacts that occur throughout the chromosome. It remains to be studied how DNA organization activities of Fis and HU that are well understood at a smaller scale (~1-kb) results in the formation of long-range DNA-DNA interactions. Nonetheless, some of the HU-mediated DNA interactions require the presence of naRNA4. naRNA4 also participates in making long-range DNA contacts. HU catalyzes some of the contacts, not all, suggesting that RNA participates with other NAPs in forming DNA contacts. HU also appears to act together with MukB to promote long-range DNA-DNA interactions. This view is based on observations that the absence of either HU or MukB caused a reduction in the same DNA-DNA contacts. It is unclear how MukB and HU potentially act together in promoting DNA-DNA interactions. It is possible that the two proteins interact physically. Alternatively, while MukBEF extrudes large DNA loops, HU condenses and organizes those loops. Role of functional relatedness of genes There are reports that functionally-related genes