E-box

The E-box was discovered in a collaboration between Susumu Tonegawa's and Walter Gilbert's laboratories in 1985 as a control element in immunoglobulin heavy-chain enhancer.

They suggested that proteins made by specific tissues acted on these enhancers to activate sets of genes during cell differentiation.

[6] Two years later, the third E-box binding protein, HEB, was discovered by screening a cDNA library from HeLa cells.

[9] In particular, several experiments have shown that the E-box is an integral part of the transcription-translation feedback loop that comprises the circadian clock.

[10] This motif consists of two amphipathic α-helices, separated by a small sequence of amino acids, that form one or more β-turns.

Depending on the DNA motif ("CAGCTG" versus "CACGTG") the bHLH protein has a different set of basic residues.

[19] A total of 320 E-box-controlled genes are found in the SCN (suprachiasmatic nucleus), liver, aorta, adrenal, WAT (white adipose tissue), brain, atria, ventricle, prefrontal cortex, skeletal muscle, BAT (brown adipose tissue), and calvarial bone.

E-box like CLOCK-related elements (EL-box; GGCACGAGGC) are also important in maintaining circadian rhythmicity in clock-controlled genes.

Furthermore, HES1, which can bind to a different consensus sequence (CACNAG, known as the N-box), shows suppression effect in EL-box, but not in E-box.

[23] It was concluded that CLOCK regulates DBP expression by binding to E-box motifs in enhancer regions located in the first and second introns.

[26] MyoD comes from the Mrf bHLH family and its main role is myogenesis, the formation of muscular tissue.

When MyoD binds to the E-box motif CANNTG, muscle differentiation and expression of muscle-specific proteins is initiated.

[27] The researchers ablated various parts of the recombinant MyoD sequence and concluded that MyoD used encompassing elements to bind the E-box and the tetralplex structure of the promoter sequence of the muscle specific gene α7 integrin and sarcomeric sMtCK.

MyoG-E-Box binding is necessary for neuromuscular synapse formation as an HDAC-Dach2-myogenin signaling pathway in skeletal muscle gene expression has been identified.

Researchers at the Medical School of Nanjing University found that the amplitude of FBXL3 (F-box/Leucine rich-repeat protein) is expressed via an E-box.

[41] These nucleotides determine the 3-D spatial arrangement of the DNA strand and restrict the size of binding transcription factors.