1. History

2. Location

3. Proposed models of LCR function
     Looping model    Tracking model    Facilitated tracking model    Linking model  

4. Diseases related to the LCR

5. References

The locus control region (LCR) is a long-range cis-regulatory element that enhances expression of linked genes at distal chromatin sites. It functions in a copy number-dependent manner and is tissue-specific, as seen in the selective expression of β-globin genes in erythroid cells.^[1] Expression levels of genes can be modified by the LCR and gene-proximal elements, such as promoters, enhancers, and silencers. The LCR functions by recruiting chromatin-modifying, coactivator, and transcription complexes.^[2] Its sequence is conserved in many vertebrates, and conservation of specific sites may suggest importance in function.^[2]

History

The LCR was identified over 20 years ago in studies of transgenic mice. These studies determined that the LCR was required for normal regulation of beta-globin gene expression.^[3]

Evidence of the presence of this additional regulatory element came from a group of patients that lacked a 20 kb region upstream of the β-globin cluster that was vital for expression of any of the β-globin genes. Even though all of the genes themselves and the other regulatory elements were intact, without this domain, none of the genes in the β-globin cluster were expressed.^[4]

Location

Although the name implies that the LCR is limited to a single region, this implication only applies to the β-globin LCR. Other studies have found that a single LCR can be distributed in multiple areas around and inside the genes it controls.

The β-globin LCR in mice and humans is found 6–22 kb upstream of the first globin gene (epsilon).^[1][2]

Proposed models of LCR function

Although studies have been conducted to attempt to identify a model of how the LCR functions, evidence for the following models is not strongly supported or precluded.^[1]

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.^[1]

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.^[1]

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]

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.^[1]

Diseases related to the LCR

Studies in transgenic mice have shown that deletion of the β-globin LCR causes the region of chromosome to condense into a heterochromatic state.^[1][2] This leads to decreased expression of β-globin genes, which can cause β-thalassemia in humans and mice.

References

• Kŭmt‘ap-Sa Temple
• Kŭmt‘ap Temple
• Kŭmt‘ap temple
• Kŭmya Station
• Kůlna Cave
• Kơ nia
• Kơ nia almond tree
• Kơ nia tree
• Kɛlɛngaxo Bozo
• Kɯrɯ
• Kɯrɯ skɤt
• Kʼabeena
• Kʼabeena language
• Kʼan Chitam
• Kʼatepan
• Kʼinich Janaab Pakal II
• Kʼinich Kan Bahlam III
• Kʼinich Kʼukʼ Bahlam II
• Kʼinich Muwaan Jol
• Kʼàakʼ Chiʼ
• K̆
• K̈
• /k̟/
• K̲h̲ayālī
• K͡x