![Locus Control Regions
• Locus Control Regions it is bounded by transcription factors coactivators, repressors, and/or
chromatin modifiers. Each of the components differentially affects gene expression, and it is their
collective activity that functionally defines an LCR and confers proper spatial/temporal gene expression.
• A regulatory region first identified in the human beta globin locus but subsequently found in other loci.
The region is believed to regulate genetic transcription by opening remodeling chromatin structure. It
may also have enhancer activity by different mechanisms
• Looping model
• Transcription factors bind to hypersensitive site cores and cause the LCR to form a loop that can interact
with the promoter of the gene it regulates
• Tracking model
• Transcription factors bind to the LCR to form a complex. The complex moves along the DNA helix until
it can bind to the promoter of the gene it regulates. Once bound, the transcriptional apparatus increases
gene expression.
• Facilitated tracking model
• This hypothesis combines the looping and tracking models, suggesting that the transcription factors bind
to the LCR to form a loop, which then seeks and binds to the promoter of the gene it regulates.[1]](https://image.slidesharecdn.com/upstreamcontrollableelements-210202160926/85/Up-stream-controllable-elements-12-320.jpg)
Up stream controllable elements
- 1. Up stream controllable elements D.INDRAJA
- 2. • Cis-acting transcriptional regulatory elements Genes transcribed by RNA polymerase II typically contain two distinct families of cis-acting transcriptional regulatory elements: promoter distal regulatory element / Upstream controllable elements These cis-acting transcriptional regulatory elements contain recognition sites For trans-acting DNA- binding transcription factors, which function either to enhance or repress transcription promoter: It includes Core Promoter Proximal Promoter Elements distal regulatory elements: It includes Enhancers Silencers Insulators Locus Control Regions (LCR)
- 3. Promoter • promoter is a region of DNA that initiates transcription of a particular gene Promoters are located near the transcription start sites of genes. Promoters can be about 100–1000 base pairs long. • a promoter, which is composed of a core promoter and nearby (proximal) regulatory elements The core promoter is the region at the start of basic transcriptional machinery and PIC assembly, and defines the position of the TSS. The core promoter usually refers to the region from the transcription start site including the TATA box, which resides approximately 30 bp upstream of the transcriptionn initiation site. • The core promoter is a region around the TSS (+1) of a gene, which contains several DNA elements that facilitate the binding of regulatory proteins. PIC : Binding of regulatory proteins is required formation of the PIC (pre-initiation complex).
- 4. Core Promoter Metazoan core promoters are composed of: • TATA box The first described core promoter element • Initiator element (Inr) the most common element • Downstream Promoter Element (DPE) • Downstream Core Element (DCE) • TFIIB-Recognition Element (BRE) • Motif Ten Element (MTE).
- 5. • Proximal Promoter Elements In Metazon, several other promoter elements exist which are located upstream of the core promoter: the proximal promoter elements The proximal promoter is defined as the region immediately upstream (up to a few hundred base pairs) from the core promoter, and typically contains multiple binding sites for activators.
- 7. Enhancers • Enhancers increase the rate of transcription of genes • Enhancers enhancer is a short (50-1500 bp) region of DNA that can be bound with proteins (activators) to activate transcription of a gene or genes. These proteins are usually referred to as transcription factors • Enhancers were characterised almost 20 years ago. • Enhancers are typically composed of a cluster of TFBSs that work cooperatively to enhance transcription and • The transcription factors that bind to enhancers are called transcriptional activators • Enhancers location These enhancer regions can be found: up- and downstream of the TSS within exons or introns in the 5 and 3 untranslated (UTR) regions of genes
- 8. • When a DNA -bending protein binds to the enhancer, the shape of the DNA changes, which allows interactions between the activators and transcription factors to occur silencer • a silencer is a DNA sequence capable of binding transcription regulation factors, called repressors. • When a repressor protein binds to the silencer region of DNA, RNA polymerase is prevented from transcribing the DNA sequence into RNA. • With transcription blocked, the translation of RNA into proteins is impossible. Thus, silencers prevent genes from being expressed as proteins
- 9. Location • A silencer is a sequence-specific element that induces a negative effect on the transcription of its particular gene. • There are many positions in which a silencer element can be located in DNA. • The most common position is found upstream of the target gene where it can help repress the transcription of the gene. • This distance can vary greatly between approximately -20 bp to -2000 bp upstream of a gene. • Certain silencers can be found downstream of a promoter located within the intron or exon of the gene itself. • Silencers have also been found within the 3 prime untranslated region (3' UTR) of mRNA
- 10. Insulators • Insulators are DNA sequence elements that help to prevent inappropriate interactions between adjacent regions of the genome. • There are two types of insulator — one that is involved in enhancer-blocking activity and other that provides a barrier to the spread of heterochromatin — each with distinct functions, protein components and mechanisms. • Enhancer-blocking insulators:- • Enhancer-blocking insulators can prevent an enhancer from interacting with a promoter when placed between the two. This activity is position dependent; enhancer-blocking elements do not affect transcription from a flanking position.
- 11. • Barrier insulators:- • Barrier insulators protect transgenes against chromatin-mediated silencing. • Barrier insulators work by altering the local balance of chromatin components in a way that favours the formation of 'active' euchromatin and/or prevents the spread of 'silenced' heterochromatic structures. • Barriers achieve this by increasing the local concentration of factors that promote euchromatin formation either by direct recruitment or by tethering the insulator site to a subnuclear compartment that is rich in these factors.
- 12. Locus Control Regions • Locus Control Regions it is bounded by transcription factors coactivators, repressors, and/or chromatin modifiers. Each of the components differentially affects gene expression, and it is their collective activity that functionally defines an LCR and confers proper spatial/temporal gene expression. • A regulatory region first identified in the human beta globin locus but subsequently found in other loci. The region is believed to regulate genetic transcription by opening remodeling chromatin structure. It may also have enhancer activity by different mechanisms • Looping model • Transcription factors bind to hypersensitive site cores and cause the LCR to form a loop that can interact with the promoter of the gene it regulates • Tracking model • Transcription factors bind to the LCR to form a complex. The complex moves along the DNA helix until it can bind to the promoter of the gene it regulates. Once bound, the transcriptional apparatus increases gene expression. • Facilitated tracking model • This hypothesis combines the looping and tracking models, suggesting that the transcription factors bind to the LCR to form a loop, which then seeks and binds to the promoter of the gene it regulates.[1]
- 13. • Linking model • Transcription factors bind to DNA from the LCR to the promoter in an orderly fashion using non-DNA- binding proteins and chromatin modifiers. This changes chromatin conformation to expose the transcriptional domain. Locus Control Regions location • Although LCRs are typically located upstream of their target gene(s), they can also be found within: intron of the gene they regulate, exemplified by the human adenosine deaminase LCR downstream of the gene, as in the case of the CD2 or Th2 LCR in the intron of a neighboring gene, as occurs with the CD4 LCR