====== Cis-regulatory element ======


Cis-regulatory elements (CREs) are regions of [[noncoding DNA]] which regulate the transcription of neighboring genes. CREs are vital components of [[Gene regulatory network]]s, which in turn control morphogenesis, the development of anatomy, and other aspects of embryonic development, studied in evolutionary developmental biology.

CREs are found in the vicinity of the genes that they regulate. CREs typically regulate gene transcription by binding to transcription factors. A single transcription factor may bind to many CREs, and hence control the expression of many genes (pleiotropy). The Latin prefix cis means "on this side", i.e. on the same molecule of DNA as the gene(s) to be transcribed. CREs are often but not always upstream of the transcription site.

CREs contrast with trans-regulatory elements (TREs). TREs code for transcription factors.
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RET [[finger protein]] (RFP) forms a complex with [[histone deacetylase 1]], resulting in aberrant [[deacetylation]] of [[H3K27ac]] and dysregulation of [[cis-regulatory element]]s. 

Ranjit et al., evaluated the modulatory effects of RFP knockdown on cis-regulatory elements, [[gene expression]], and [[chemosensitivity]] to [[temozolomide]] both in [[glioblastoma cell]]s and in an intracranial [[glioblastoma]] [[model]]. The combination of RFP knockdown and temozolomide treatment markedly suppressed the glioblastoma cell growth due to [[oxidative stress]] and aberrant [[cell cycle]] and increased survival time in mice with [[glioblastoma]]. ChIP-seq and RNA-seq revealed that RFP knockdown increased or decreased activity of numerous cis-regulatory elements that lie adjacent to genes that control functions such as [[apoptosis]], [[mitosis]], [[DNA replication]], and [[cell cycle]]: [[FOXO1]], [[TBP2]], and [[PARPBP]]. This study suggests that RFP contributes to chemoresistance via aberrant deacetylation of [[histone H3]] at [[K27]], whereas dysregulation of RFP-associated cis-regulatory elements in glioma and RFP knockdown combined with temozolomide is an effective treatment strategy for lethal [[glioma]]
((Ranjit M, Hirano M, Aoki K, Okuno Y, Ohka F, Yamamichi A, Kato A, Maeda S,
Motomura K, Matsuo K, Enomoto A, Ino Y, Todo T, Takahashi M, Wakabayashi T, Kato 
T, Natsume A. Aberrant Active cis-Regulatory Elements Associated with
Downregulation of RET Finger Protein Overcome Chemoresistance in Glioblastoma.
Cell Rep. 2019 Feb 26;26(9):2274-2281.e5. doi: 10.1016/j.celrep.2019.01.109.
PubMed PMID: 30811978.
)).