![]() | This is a user sandbox of
Jvand258. You can use it for testing or practicing edits. This is not the sandbox where you should draft your assigned article for a dashboard.wikiedu.org course. To find the right sandbox for your assignment, visit your Dashboard course page and follow the Sandbox Draft link for your assigned article in the My Articles section. |
In genetics, repression is a mechanism often used to decrease or inhibit the expression of a gene. Removal of repression is called derepression. This mechanism may occur at different stages in the central dogma, with the result of increasing the overall RNA or protein products in the cell. Dysregulation of derepression can result in altered gene expression patterns and negative phenotypic consequences, such as disease.
Transcription can be repressed in a variety of ways, and therefore can be derepressed in different ways as well. A common mechanism is a substrate causing a conformational change in a repressor protein bound upstream of a gene, such as in an operator sequence. This allosteric regulation would take away the repressor’s ability to bind DNA, thus removing the repressive effect on transcription [CITE].
Another form of transcriptional derepression uses chromatin remodeling complexes. For transcription to occur, RNA polymerase needs to have access to the promoter sequence of the gene. Sometimes these sequences are wrapped around nucleosomes or are in condensed heterochromatin regions, and are therefore inaccessible. Through the mechanism of chromatin remodeling these promoter sequences can become accessible to the RNA polymerase, and transcription becomes derepressed [CITE].
Transcriptional derepression may also occur at the level of transcription factor activation. Certain families of transcription factors are non-functional on their own because their catalytic domains are blocked by another part of the protein [CITE]. Substrate binding to this second, regulatory domain causes a conformational change which allows access to the catalytic domain [CITE]. This allows the transcription factor to bind the DNA and serve its function, thus derepressing the gene.
Derepression of translation increases protein production without altering the levels of mRNA in the cell. miRNAs are a common mechanism of translation repression, binding to the mRNA through complimentary base pairing to silence them [CITE]. Certain RNA binding proteins have been shown to target untranslated regions of the mRNAs and upregulate the translation initiation rates by alleviating the repressive miRNA effects [CITE].
Another example is the auxin mediated derepression of the auxin response factor family of transcription factors in plants. These auxin response factors are repressed by Aux/IAA repressors. In the presence of auxin, these Aux/AII proteins undergo ubiquitination and are then degraded [CITEx2]. This derepresses the auxin response factors so they may carry out their functions in the cell.
Alzheimer’s is a neurodegenerative disease involving progressive memory loss and other declines in function. One common cause of familial Alzheimer’s is mutations in the PSEN1 gene.[CITE] This gene encodes a protein that cleaves intracellular peptides, which promotes CBP degradation in the cytoplasm. Mutations in PSEN1 decrease the amount of cleavage occurring, thus derepressing CBP’s ability to upregulate transcription of certain other genes. [CITE]
Rhett syndrome is a neurodevelopmental disorder involving deterioration of learned language and motor skills, autism, and seizures. Many cases of Rhett syndrome are associated with mutations in MECP2, a gene encoding a transcriptional repressor.[CITE] Mutations in this gene decrease the levels of MeCP2 binding to different promoter sequences, derepressing them. The increased expression of these MeCP2 regulated genes in neurons contribute to the Rhett syndrome phenotype. [CITEx2]
This syndrome is associated with an increased susceptibility of tumors and growth abnormalities in children. A common mutation causing this syndrome is in an imprint control region near the Igf2 gene.[CITE] This imprint control region is normally bound by an insulator which represses an enhancer from acting on the Igf2 gene on the maternal allele, but is absent and allows access on the paternal allele. Mutations in this imprint control gene inhibit the insulator from binding, which derepresses enhancer activity on the maternal allele. This abnormal derepression and increase in gene expression is a cause of Beckwith-Wiedemann syndrome. [CITE]
Changes
Sources [1] [2] [3] [4] [5] [6] [7] [8] [9] .
{{
cite journal}}
: CS1 maint: PMC format (
link)
Derepression (the topic I am assigned to)
![]() | This is a user sandbox of
Jvand258. You can use it for testing or practicing edits. This is not the sandbox where you should draft your assigned article for a dashboard.wikiedu.org course. To find the right sandbox for your assignment, visit your Dashboard course page and follow the Sandbox Draft link for your assigned article in the My Articles section. |
In genetics, repression is a mechanism often used to decrease or inhibit the expression of a gene. Removal of repression is called derepression. This mechanism may occur at different stages in the central dogma, with the result of increasing the overall RNA or protein products in the cell. Dysregulation of derepression can result in altered gene expression patterns and negative phenotypic consequences, such as disease.
Transcription can be repressed in a variety of ways, and therefore can be derepressed in different ways as well. A common mechanism is a substrate causing a conformational change in a repressor protein bound upstream of a gene, such as in an operator sequence. This allosteric regulation would take away the repressor’s ability to bind DNA, thus removing the repressive effect on transcription [CITE].
Another form of transcriptional derepression uses chromatin remodeling complexes. For transcription to occur, RNA polymerase needs to have access to the promoter sequence of the gene. Sometimes these sequences are wrapped around nucleosomes or are in condensed heterochromatin regions, and are therefore inaccessible. Through the mechanism of chromatin remodeling these promoter sequences can become accessible to the RNA polymerase, and transcription becomes derepressed [CITE].
Transcriptional derepression may also occur at the level of transcription factor activation. Certain families of transcription factors are non-functional on their own because their catalytic domains are blocked by another part of the protein [CITE]. Substrate binding to this second, regulatory domain causes a conformational change which allows access to the catalytic domain [CITE]. This allows the transcription factor to bind the DNA and serve its function, thus derepressing the gene.
Derepression of translation increases protein production without altering the levels of mRNA in the cell. miRNAs are a common mechanism of translation repression, binding to the mRNA through complimentary base pairing to silence them [CITE]. Certain RNA binding proteins have been shown to target untranslated regions of the mRNAs and upregulate the translation initiation rates by alleviating the repressive miRNA effects [CITE].
Another example is the auxin mediated derepression of the auxin response factor family of transcription factors in plants. These auxin response factors are repressed by Aux/IAA repressors. In the presence of auxin, these Aux/AII proteins undergo ubiquitination and are then degraded [CITEx2]. This derepresses the auxin response factors so they may carry out their functions in the cell.
Alzheimer’s is a neurodegenerative disease involving progressive memory loss and other declines in function. One common cause of familial Alzheimer’s is mutations in the PSEN1 gene.[CITE] This gene encodes a protein that cleaves intracellular peptides, which promotes CBP degradation in the cytoplasm. Mutations in PSEN1 decrease the amount of cleavage occurring, thus derepressing CBP’s ability to upregulate transcription of certain other genes. [CITE]
Rhett syndrome is a neurodevelopmental disorder involving deterioration of learned language and motor skills, autism, and seizures. Many cases of Rhett syndrome are associated with mutations in MECP2, a gene encoding a transcriptional repressor.[CITE] Mutations in this gene decrease the levels of MeCP2 binding to different promoter sequences, derepressing them. The increased expression of these MeCP2 regulated genes in neurons contribute to the Rhett syndrome phenotype. [CITEx2]
This syndrome is associated with an increased susceptibility of tumors and growth abnormalities in children. A common mutation causing this syndrome is in an imprint control region near the Igf2 gene.[CITE] This imprint control region is normally bound by an insulator which represses an enhancer from acting on the Igf2 gene on the maternal allele, but is absent and allows access on the paternal allele. Mutations in this imprint control gene inhibit the insulator from binding, which derepresses enhancer activity on the maternal allele. This abnormal derepression and increase in gene expression is a cause of Beckwith-Wiedemann syndrome. [CITE]
Changes
Sources [1] [2] [3] [4] [5] [6] [7] [8] [9] .
{{
cite journal}}
: CS1 maint: PMC format (
link)
Derepression (the topic I am assigned to)