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Kruppel-like factors
In molecular genetics, the Krüppel-like family of transcription factors (KLFs) are a set of eukaryotic Cys2His2 zinc finger DNA-binding proteins that regulate gene expression. This family has been expanded to also include the Sp transcription factor and related proteins, forming the Sp/KLF family.
The following human genes encode Kruppel-like factors: KLF1, KLF2, KLF3, KLF4, KLF5, KLF6, KLF7, KLF8, KLF9, KLF10, KLF11, KLF12, KLF13, KLF14, KLF15, KLF16, KLF17
The following genes are Sp factors: Sp1, Sp2, Sp3, Sp4, Sp5, Sp6, Sp7, Sp8, and Sp9.
Note that although KLF14 was an alias for Sp6 (Q3SY56), it now refers to a protein (Q8TD94) derived from KLF16 by a retrotransposon event.
KLF/Sps are a family of transcription factors that contain three carboxyl-terminal (C-terminal) Cys2His2-type zinc finger structural motifs that bind to the GC-rich regions in DNA and regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. The C-terminal end binds to the promoter and enhancer regions of a gene. Each KLF also has a unique amino-terminal (N-terminal) end that acts as the functional domain that allows it to bind specifically to a certain partner. KLFs share the similar function of transcription regulation via the recruitment of regulatory proteins. These transcription factors have a conserved structural homology between mammalian species, which allow for similar function due to similar protein interaction motifs at the N-terminal domains. The C-terminal end is also highly conserved with both the first and second zinc finger have 25 amino acids, while the third has 23 amino acids. Each of the three zinc fingers recognize three unique base pairs for their DNA-binding sites, which together make the general form NCR CRC CCN (where N is any base and R is a purine). There is some evidence that positively-charged amino acids within the three zinc fingers may contribute towards localizing the protein in the Nucleus. The N-terminal end allows for the binding of various coactivators, corepressors, and modifiers. All family members share the zinc finger signature KLF-DBD of CxxxxCxxxxxxxxxxxxHxxxHxxxxxxxCxxxxCxxxxxxxxxxxxHxxxHxxxxxxxCxxCxxxxxxxxxxxxHxxxH and use a 9aaTAD.
KLFs are divided into three subgroups; Group 1 (KLF 3,8, and 12) are repressors via interaction with the C-terminal Binding Protein 1 and 2 (CtBP1 and CtBP2). Group 2 (KLFs 1,2,4,5,6, and 7) are transcription activators. Group 3 (KLFs 9,10,11,13,12, and 16) have repressor activity via interaction with the common transcriptional co-repressor, Sin3A. KLFs 15 and 17 are distantly related without any defined protein interaction motifs.
The Sp family members diverged from KLFs since Filozoa. They are typically divided into two groups of Sp1-4 and Sp5-9. One of the signatures is the "Btd box" CxCPxC preceding the KLF-DBD.
The proliferation of KLF genes, presumably from an ancestral KLF, is also interesting. In some cases different family members are expressed in different tissues. The first KLF, KLF1, originally known as Erythroid KLF (EKLF) is expressed only in red blood cells and megakaryocytes. It drives red blood cell differentiation and represses megakaryocyte formation. It appears that it has arisen as a KLF family member that has a particular role in these two blood lineages. Other KLFs are more broadly expressed and there are interactions between family members. KLF3 for instance is driven by KLF1 as is KLF8. On the other hand, KLF3 represses KLF8. Such cross-regulation occurs extensively in transcription factor families. Many transcription factor genes regulate their own promoters and when a gene duplicates during evolution then cross-regulation often occurs. The cross-regulation can ensure that the total amount of KLFs in the cell is monitored and controlled.
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Kruppel-like factors
In molecular genetics, the Krüppel-like family of transcription factors (KLFs) are a set of eukaryotic Cys2His2 zinc finger DNA-binding proteins that regulate gene expression. This family has been expanded to also include the Sp transcription factor and related proteins, forming the Sp/KLF family.
The following human genes encode Kruppel-like factors: KLF1, KLF2, KLF3, KLF4, KLF5, KLF6, KLF7, KLF8, KLF9, KLF10, KLF11, KLF12, KLF13, KLF14, KLF15, KLF16, KLF17
The following genes are Sp factors: Sp1, Sp2, Sp3, Sp4, Sp5, Sp6, Sp7, Sp8, and Sp9.
Note that although KLF14 was an alias for Sp6 (Q3SY56), it now refers to a protein (Q8TD94) derived from KLF16 by a retrotransposon event.
KLF/Sps are a family of transcription factors that contain three carboxyl-terminal (C-terminal) Cys2His2-type zinc finger structural motifs that bind to the GC-rich regions in DNA and regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. The C-terminal end binds to the promoter and enhancer regions of a gene. Each KLF also has a unique amino-terminal (N-terminal) end that acts as the functional domain that allows it to bind specifically to a certain partner. KLFs share the similar function of transcription regulation via the recruitment of regulatory proteins. These transcription factors have a conserved structural homology between mammalian species, which allow for similar function due to similar protein interaction motifs at the N-terminal domains. The C-terminal end is also highly conserved with both the first and second zinc finger have 25 amino acids, while the third has 23 amino acids. Each of the three zinc fingers recognize three unique base pairs for their DNA-binding sites, which together make the general form NCR CRC CCN (where N is any base and R is a purine). There is some evidence that positively-charged amino acids within the three zinc fingers may contribute towards localizing the protein in the Nucleus. The N-terminal end allows for the binding of various coactivators, corepressors, and modifiers. All family members share the zinc finger signature KLF-DBD of CxxxxCxxxxxxxxxxxxHxxxHxxxxxxxCxxxxCxxxxxxxxxxxxHxxxHxxxxxxxCxxCxxxxxxxxxxxxHxxxH and use a 9aaTAD.
KLFs are divided into three subgroups; Group 1 (KLF 3,8, and 12) are repressors via interaction with the C-terminal Binding Protein 1 and 2 (CtBP1 and CtBP2). Group 2 (KLFs 1,2,4,5,6, and 7) are transcription activators. Group 3 (KLFs 9,10,11,13,12, and 16) have repressor activity via interaction with the common transcriptional co-repressor, Sin3A. KLFs 15 and 17 are distantly related without any defined protein interaction motifs.
The Sp family members diverged from KLFs since Filozoa. They are typically divided into two groups of Sp1-4 and Sp5-9. One of the signatures is the "Btd box" CxCPxC preceding the KLF-DBD.
The proliferation of KLF genes, presumably from an ancestral KLF, is also interesting. In some cases different family members are expressed in different tissues. The first KLF, KLF1, originally known as Erythroid KLF (EKLF) is expressed only in red blood cells and megakaryocytes. It drives red blood cell differentiation and represses megakaryocyte formation. It appears that it has arisen as a KLF family member that has a particular role in these two blood lineages. Other KLFs are more broadly expressed and there are interactions between family members. KLF3 for instance is driven by KLF1 as is KLF8. On the other hand, KLF3 represses KLF8. Such cross-regulation occurs extensively in transcription factor families. Many transcription factor genes regulate their own promoters and when a gene duplicates during evolution then cross-regulation often occurs. The cross-regulation can ensure that the total amount of KLFs in the cell is monitored and controlled.