regulatory region. The transcriptional region is the part of DNA to betranscribedinto a primary transcript (an RNA molecule complementary to the transcriptional region). The regulatory region can be divided intocis- regulatory(or cis-acting) elements andtrans- regulatory(or trans-acting) elements. The cis-regulatory elements are the binding sites oftranscription factorswhich are the proteins that, upon binding with cis-regulatory elements, can affect (either enhance or repress) transcription.
The cis-acting elements may be divided into the
following four types:-(1)Promoter. (2)Enhancer. (3)Silencer. (4)Response element. (1)Promoter Promoteris the DNA region where the transcription initiation takes place. In prokaryotes, the sequence of a promoter is recognized by thesigma () factorof the RNA polymerase. In eukaryotes, it is recognized by E. coli specifictranscription factors. E. colihas five sigma factors: Sigma 70: Regulate expression of most genes. Sigma 32: Regulate expression of heat shock proteins. Sigma 28: Regulate expression of flagellar operon (involved in cell motion). Sigma 38: Regulate gene expression against Eukaryotes The most common promoter element in eukaryotic protein genes is theTATA box, located at -35 to -20. Its consensus sequence,TATAAA, is quite similar to the -10 region of the Sigma 70 recognition site. Another promoter element is called theinitiator(Inr). It has the consensus sequence PyPyAN(T/A)PyPy, where Py denotes pyrimidine (C or T), N = any, and (T/A) means T or A. The base A at the third position is located at +1 (the transcriptional start site). TATA box and initiator are thecore promoter elements. There are other elements often located within The protein which interacts with the initiator and TATA box is known as theTATA-box binding protein (TBP), which recognizes not only the core promoter of protein genes, but also RNA promoters. It is a subunit of the general transcription factor TFIID. In eukaryotes, transcription requires several different general transcription factors and, in most cases, the regulatory transcription factors. Example: thepromoter region of theIL-2gene, which contains TATA box and the binding sites of transcription factors, NFAT, Oct-1, NF-B and AP- (2)Enhancer The element that, upon binding with transcription factors, can enhance transcription. The transcription factors that bind to enhancers are calledtranscriptional activators. It may be located either upstream or downstream of the transcriptional initiation site. However, most of them are located upstream. In prokaryotes, enhancers are quite close to the promoter, but eukaryotic enhancers could be far from the promoter. A few examples are given below. E. coli glnAgene
The enhancer of theglnAgene is located about
120 bp from the start site, containing two binding sites for the transcription factor nitrogen regulatory protein C(NTRC). YeastGAL1andGA L10genes
BothGAL1andGAL10genes are regulated by
the same enhancer between them. The two genes are transcribed along opposite directions. Therefore, the enhancer is located upstream of both transcriptional start sites. It is also calledupstream activating sequences(UAS), Human globin gene cluster
The human globin gene cluster is controlled
by an enhancer region comprising HS1 to HS4, which contain the binding sites of GATA-1, NF-E2, AP-1 and other transcriptional activators. This region is known as thelocus control region(LCR), which regulates the expression of all five genes(, G, A, and ), even though the distance between HS4 and the gene is as far as 60 kb. Examples of transcriptional activators in mammals Transcripti Transcriptio Consensus Consensus on n Sequence Sequence Activator Activator PuGPuCATG AP-1 TGAGTCA p53 PyCPy CCC(A/C)N(C GGGPuNTP AP-2 NF-kB /G)3 yPyCC Oct-1 ATGCAAAT NFAT GGAGAPu GATA-1 (A/T)GATAPu NF-E2 TGACTCA *Pu = Purine (A or G); Py = Pyrimidine (C or T); N = any. (3)Silencer The element that, upon binding with transcription factors, can repress transcription. The transcription factors that bind to silencers are calledrepressors. In prokaryotes, silencers are known asoperators, found in many genes such aslacoperon andtrpoperon. In eukaryotes, the following genes have been demonstrated to contain silencers:-(i)Human globin gene (ii)Human CD95(Fas/APO-1) gene. (iii)Human dopamine beta-hydroxylase (DBH) gene. In a few cases, a DNA element may act either as an enhancer or a silencer, depending on the binding protein. For example, certain genes contain an element calledE box(consensus CACGTG) which can bind either Max/Myc dimer or Max/Mad dimer. The Max/Myc dimer activates transcription, whereas the Max/Mad dimer suppresses (4)Response element transcription of these genes.
The recognition site of certain transcription
factors. Most of them are located within 1 kb from the transcriptional start site. Eukaryotic response elements Response Transcription Consensus Element Factor Sequence CRE CREB TGACGTCA Estrogen AGGTCANNNT ERE receptor GACCT Glucocorticoid AGAACANNNT GRE receptor GTTCT Heat shock GAANNTTCNN HSE factor GAA Serum SRE response CC(A/T)6GG factor *(A/T)6means six A or T; N = any. The cAMP response element (CRE) interacts with CREB (CRE-binding protein), which is regulated by cAMP. Estrogen response element (ERE) and glucocorticoid response element (GRE) are the recognition sites of estrogen receptor and glucocorticoid receptor, respectively. Heat shock response element (HSE) is present in heat shock protein genes. In response to external stress (e.g. high temperature), the heat shock factor (HSF) will interact with HSE, stimulating expression of heat shock proteins. Serum response element (SRE) binds to serum response factor (SRF), which can be activated by many growth factors in serum. The Fos subunit ofAP-1is encoded by a gene containing SRE. Fos is known to play an important role in cell cycle progression.
Alveolar Bone Grafting Techniques For Dental Implant Preparation, An Issue of Oral and Maxillofacial Surgery Clinics - Saunders 1 Edition (September 21, 2010)