Gene transcriptions/Distal promoters

(Redirected from Distal promoter)

A distal promoter is a distant (in numbers of nucleotides) portion of the promoter for a particular gene.

This distal sequence is upstream of the gene.

It is a region of DNA that may contain additional regulatory elements, often with a weaker influence than the proximal promoter.



A promoter is a region of DNA that facilitates the transcription of a particular gene. "Promoters can be about 100–1000 [nucleotides] long.[1]

A promoter is on the template strand for the gene and near the gene in numbers of nucleotides (nts) along the DNA template strand. Usually, the promoter lies within the string of nucleotides between genes.

Some promoters are called constitutive as they are active in all circumstances in the cell, while others are regulated becoming active in response to specific stimuli.

These specific stimuli for a gene find a receptive portion within that gene's promoter.

In the case of genes that are used to produce proteins, the RNA polymerase II holoenzyme that actually performs the transcription from the template strand needs to find chemical cues for attachment to the DNA and where to begin transcription. Preceding this are chemical cues for which DNA strand is the template strand and in what direction transcription is to be performed.

A promoter contains cues for the number of copies to be transcribed and when to stop making copies.

Once the holoenzyme is assembled and attached to the promoter, the transcription start site (TSS) is transcribed as the first nucleotide of the pre-messenger RNA.

When a transcription factory is nearby, chemical cues begin the movement of the euchromatin to the factory. The already assembled RNA polymerase II holoenzyme attaches per appropriate cues and begins transcription at the designated TSS. Some genes have more than one TSS.



Def. remote "from the point of attachment or origin"[2] is called distal.

Theoretical distal promoters


Here's a theoretical definition:

Def. an upstream region between -2.0 knts to -1.5 knts for a gene that can exist in a supercoiled conformation with this region to be actively transcribed is called a distal promoter.



The "upstream regions of the human CYP11A and bovine CYP11B genes [have] a distal promoter in each gene. The distal promoters are located at −1.8 to −1.5 kb in the upstream region of the CYP11A gene and −1.5 to −1.1 kb in the upstream region of the CYP11B gene."[3]

βA-globin genes


"Using cloned chicken βA-globin genes, either individually or within the natural chromosomal locus, enhancer-dependent transcription is achieved in vitro at a distance of 2 kb with developmentally staged erythroid extracts. This occurs by promoter derepression and is critically dependent upon DNA topology. In the presence of the enhancer, genes must exist in a supercoiled conformation to be actively transcribed, whereas relaxed or linear templates are inactive. Distal protein–protein interactions in vitro may be favored on supercoiled DNA because of topological constraints."[4]



Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide, also known as FCER1A, is a protein which in humans is encoded by the FCER1A gene.[5]

The human FCER1A may be regulated using its distal promoter.[6]



Hemoglobin subunit epsilon is a protein that in humans is encoded by the HBE1 gene.[7]

There is a G to A substitution in the distal CCAAT box of the A gamma-globin gene in Greek hereditary persistence of fetal haemohlobin.[8]

The distal promoter element ACACCC has a role regarding base substitution at position -88 in a beta-thalassemic globin gene.[9]



Histone H1.2 is a protein that in humans is encoded by the HIST1H1C gene.[10][11][12]

A distal promoter in the S-phase has a role in the control of the human H1.2 histone gene transcription.[13]



In humans, prolactin is produced at least in the pituitary, decidua, myometrium, breast, lymphocytes, leukocytes and prostate.[14][15]

Pituitary PRL is controlled by the Pit-1 transcription factor and ultimately dopamine, extrapituitary PRL is controlled by a superdistal promoter and apparently unaffected by dopamine.[15]

In decidual cells and in lymphocytes the distal promoter and thus prolactin expression is stimulated by [cyclic adenosine monophosphate] cAMP. [Responsiveness] to cAMP is mediated by an imperfect cAMP–responsive element and two CAAT/enhancer binding proteins (C/EBP).[15] Progesterone has been observed to upregulate prolactin synthesis in the endometrium but decreases it in myometrium and breast glandular tissue.[16] However breast and other tissues may also express the Pit-1 promoter in addition to the distal promoter.



"This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus."[17]



Six3OS1 is a long non-coding RNA. It was originally identified in the murine embryonic and postnatal retina.[18] It is located in the distal promoter region of the gene encoding Six3, a homeodomain transcription factor. It regulates the activity of Six3 in the developing mouse retina, by binding to transcriptional co-regulators of Six3 and to histone modification enzymes and acting as a transcriptional scaffold.[19]

See also



  1. "Analysis of Biological Networks: Transcriptional Networks - Promoter Sequence Analysis" (PDF). Tel Aviv University. Retrieved 30 December 2012.
  2. Poccil (18 October 2004). "distal". San Francisco, California: Wikimedia Foundation, Inc. Retrieved 2014-05-29. {{cite web}}: |author= has generic name (help)
  3. Koichi Takayama, Ken-ichirou Morohashi, Shin-ichlro Honda, Nobuyuki Hara and Tsuneo Omura (1 July 1994). "Contribution of Ad4BP, a Steroidogenic Cell-Specific Transcription Factor, to Regulation of the Human CYP11A and Bovine CYP11B Genes through Their Distal Promoters". The Journal of Biochemistry 116 (1): 193–203. doi:10.1093/oxfordjournals.jbchem.a124493. Retrieved 2017-08-16. 
  4. Michelle Craig Barton, Navid Madani, and Beverly M. Emerson (8 July 1997). "Distal enhancer regulation by promoter derepression in topologically constrained DNA in vitro". Proceedings of the National Academy of Sciences of the United States of America 94 (14): 7257-62. Retrieved 2017-08-16. 
  5. Pang J, Taylor GR, Munroe DG, Ishaque A, Fung-Leung WP, Lau CY, Liu FT, Zhou L (December 1993). "Characterization of the gene for the human high affinity IgE receptor (Fc epsilon RI) alpha-chain". Journal of Immunology 151 (11): 6166–74. PMID 8245459. 
  6. Hasegawa M, Nishiyama C, Nishiyama M, et al. (2003). "Regulation of the human Fc epsilon RI alpha-chain distal promoter". Journal of Immunology 170 (7): 3732–8. PMID 12646639. 
  7. Higgs DR, Vickers MA, Wilkie AO, Pretorius IM, Jarman AP, Weatherall DJ (May 1989). "A review of the molecular genetics of the human alpha-globin gene cluster". Blood 73 (5): 1081–104. PMID 2649166. 
  8. Gelinas R, Endlich B, Pfeiffer C, et al. (1985). "G to A substitution in the distal CCAAT box of the A gamma-globin gene in Greek hereditary persistence of fetal haemoglobin". Nature 313 (6000): 323–5. doi:10.1038/313323a0. PMID 2578619. 
  9. Orkin SH, Antonarakis SE, Kazazian HH (1984). "Base substitution at position -88 in a beta-thalassemic globin gene. Further evidence for the role of distal promoter element ACACCC". J. Biol. Chemistry 259 (14): 8679–81. PMID 6086605. 
  10. Eick S, Nicolai M, Mumberg D, Doenecke D (September 1989). "Human H1 histones: conserved and varied sequence elements in two H1 subtype genes". European Journal of Cell Biology 49 (1): 110–5. PMID 2759094. 
  11. Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ (October 2002). "The human and mouse replication-dependent histone genes". Genomics 80 (5): 487–98. doi:10.1016/S0888-7543(02)96850-3. PMID 12408966. 
  12. "Entrez Gene: HIST1H1C histone cluster 1, H1c".
  13. Eilers A, Bouterfa H, Triebe S, Doenecke D (1994). "Role of a distal promoter element in the S-phase control of the human H1.2 histone gene transcription". European Journal of Biochemistry 223 (2): 567–74. doi:10.1111/j.1432-1033.1994.tb19026.x. PMID 8055927. 
  14. . PMID 8969972. 
  15. 15.0 15.1 15.2 . PMID 16998840. 
  16. Zinger M, McFarland M, and Ben-Jonathan N (February 2003). "Prolactin expression and secretion by human breast glandular and adipose tissue explants". Journal of Clinical Endocrinology and Metabolism 88 (2): 689-96. PMID 12574200. Retrieved 2014-05-29. 
  17. "SCP2". San Francisco, California: Wikimedia Foundation, Inc. March 17, 2013. Retrieved 2013-04-18.
  18. Alfano G, Vitiello C, Caccioppoli C, Caramico T, Carola A, Szego MJ et al. (2005). "Natural antisense transcripts associated with genes involved in eye development". Hum Mol Genet 14 (7): 913–23. doi:10.1093/hmg/ddi084. PMID 15703187. 
  19. Rapicavoli NA, Poth EM, Zhu H, Blackshaw S (2011). "The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity". Neural Development 6: 32. doi:10.1186/1749-8104-6-32. PMID 21936910. PMC 3191369. //