What is CTCF binding site?
CTCF binds together strands of DNA, thus forming chromatin loops, and anchors DNA to cellular structures like the nuclear lamina. It also defines the boundaries between active and heterochromatic DNA.
What is a CTCF insulator?
One of exceptional role of CTCF involves its insulator function. Insulators are short nucleotide sequences that set boundaries between nearby genomic domains. 9. When CTCF binds to an insulator sequence, the conversation between an enhancer and a gene promoter is impeded and transcription of the gene is blocked.
How is splicing controlled?
Splicing is regulated by trans-acting proteins (repressors and activators) and corresponding cis-acting regulatory sites (silencers and enhancers) on the pre-mRNA. However, as part of the complexity of alternative splicing, it is noted that the effects of a splicing factor are frequently position-dependent.
What is CTCF gene mutation?
Germline CTCF mutations are responsible for a specific phenotype in humans [5]; this phenotype is syndromic intellectual disability with microcephaly and growth retardation; the reported mutations are frameshift and missense mutations, which goes along with the results reported here.
What are the most probable consequences of mutations in some CTCF binding sites of the genome?
Disruption of CTCF binding at specific gene loci can lead to aberrant expression of cancer-related genes. For example, tumor-derived CTCF mutants lost the binding affinity to growth-regulatory genes such as Myc, ARF and Igf2 (insulin-like growth factor 2) [168].
What does alternative splicing allow for?
Alternative splicing is used in particular to introduce or remove a protein domain or a regulator element, allowing the change of the corresponding protein or a modification in its expression.
How are CTCF binding sites arranged?
noticed that the CTCF binding sites that form loops between promoters and enhancers are arranged in a convergent orientation. Using the CRISPR-Cas9 genome editing system they create inversions of key CTCF binding sites, switching their orientation.
How does alternative splicing regulate gene expression?
Alternative splicing can regulate protein composition by changing the coding content between isoforms of the same gene. As a consequence, AS contributes to increased protein diversity and, ultimately, cellular and functional complexity, without increasing the size of a eukaryotic organism’s genome (Stamm et al., 2005).
What sequence or sequences contribute to regulation of alternative splicing?
Additional sequences are designated as splicing enhancers or silencers, and serine-arginine rich (SR) proteins bind these sequences to further regulate alternative splicing.
Is alternative splicing post transcriptional regulation?
After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA binding protein (RBP) that control the various steps and rates controlling events such as alternative splicing, nuclear degradation (exosome), processing, nuclear export ( …
What is the significance of alternative splicing Why is it important for us to study and understand this process?
Why is alternative splicing important? The mechanisms of alternative splicing help to explain how one gene can be encoded into numerous proteins with various functions. This complexity helps drive the cellular differentiation and diversity observed throughout biology.
What is the role of alternative splicing of CTCF in gene regulation?
Previous studies have focused on investigating the roles of the canonical isoform of CTCF in gene regulation and genome organization 13, 25; nothing has been reported about the alternative splicing of CTCF and the roles of spliced isoforms in regulating higher-order chromatin structure and cellular function.
Does CTCF have an alternatively spliced short isoform?
From our own RNA-seq data in several human cell lines (HeLa-S3 and 293T cells), we found that CTCF might have an alternatively spliced short isoform in which two exons (exons 3 and 4) are skipped, producing a truncated CTCF protein with an alternative translation start site at exon 5 26.
Is the insulator protein CTCF required for correct Hox gene expression?
The Insulator Protein CTCF Is Required for Correct Hox Gene Expression, but Not for Embryonic Development in Drosophila Insulator binding proteins (IBPs) play an important role in regulating gene expression by binding to specific DNA sites to facilitate appropriate gene regulation.
What is the role of alternative splicing in chromatin organization?
Yet, the role of alternative splicing in chromatin organization has not been widely explored, and it may be an important factor, as it may control chromatin architecture to modulate regulatory pathways that can affect cell fate or function.