ESR1:ESTG:P-TEFb recruited to paused RNA polymerase II on MYB gene

Stable Identifier
R-HSA-9012315
Type
Reaction
Species
Homo sapiens
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MYB is frequently expressed in breast cancer and its expression is correlated with ER positive tumors (Guerin et al, 1990; Kauraniemi et al, 2000). MYB expression is estrogen-responsive, but hormone-dependent control is exerted at the level of transcriptional elongation rather than initiation (Frasor et al, 2003; Carroll et al, 2006; Bender et al, 1987; Watson et al, 1988; Drabsch et al, 2007). In the absence of estrogen, RNA polymerase II stalls at a stem-loop poly-T (SL-dT) tract between within intron 1 (Drabsch et al, 2007). Upon estrogen stimulation, a complex containing estrogen, the estrogen receptor and P-TEFb (an elongation factor consisting of Cyclin T and CDK9) is recruited to an ERE near the SL-dT. P-TEFb phosphorylates serine 2 in the RNA polymerase II CTD, allowing the polymerase to continue elongating (Drabsch et al, 2007; Mitra et al, 2012; reviewed in Gonda et al, 2008; Garriga and Grana, 2004). Although EREs have been identified around the SL-dT and have been shown by ChIP to be bound by ESR1, mutation of the EREs does not abrogate estrogen-responsive MYB expression, suggesting that the estrogen receptor either binds to a non-canonical site or it interacts through another transcription factor in this reaction (Drabsch et al, 2007; Mitra et al, 2012)

Literature References
PubMed ID Title Journal Year
17690249 Mechanism of and requirement for estrogen-regulated MYB expression in estrogen-receptor-positive breast cancer cells

Drabsch, Y, Hugo, H, Zhang, R, Dowhan, DH, Miao, YR, Gewirtz, AM, Barry, SC, Ramsay, RG, Gonda, TJ

Proc. Natl. Acad. Sci. U.S.A. 2007
15276198 Cellular control of gene expression by T-type cyclin/CDK9 complexes

Garriga, J, Grana, X

Gene 2004
3498214 Differential expression of c-myb mRNA in murine B lymphomas by a block to transcription elongation

Bender, TP, Thompson, CB, Kuehl, WM

Science 1987
2181374 Strong association between c-myb and oestrogen-receptor expression in human breast cancer

Guérin, M, Sheng, ZM, Andrieu, N, Riou, G

Oncogene 1990
22492511 Estrogen receptor-α recruits P-TEFb to overcome transcriptional pausing in intron 1 of the MYB gene

Mitra, P, Pereira, LA, Drabsch, Y, Ramsay, RG, Gonda, TJ

Nucleic Acids Res. 2012
3281094 A transcriptional arrest mechanism involved in controlling constitutive levels of mouse c-myb mRNA

Watson, RJ

Oncogene 1988
18476782 Estrogen and MYB in breast cancer: potential for new therapies

Gonda, TJ, Leo, P, Ramsay, RG

Expert Opin Biol Ther 2008
11034064 MYB oncogene amplification in hereditary BRCA1 breast cancer

Kauraniemi, P, Hedenfalk, I, Persson, K, Duggan, DJ, Tanner, M, Johannsson, O, Olsson, H, Trent, JM, Isola, J, Borg, A

Cancer Res. 2000
17013392 Genome-wide analysis of estrogen receptor binding sites

Carroll, JS, Meyer, CA, Song, J, Li, W, Geistlinger, TR, Eeckhoute, J, Brodsky, AS, Keeton, EK, Fertuck, KC, Hall, GF, Wang, Q, Bekiranov, S, Sementchenko, V, Fox, EA, Silver, PA, Gingeras, TR, Liu, XS, Brown, M

Nat. Genet. 2006
12959972 Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype

Frasor, J, Danes, JM, Komm, B, Chang, KC, Lyttle, CR, Katzenellenbogen, BS

Endocrinology 2003
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