Sandbox Reserved 1491: Difference between revisions
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==2xml - KDM4C catalytic domain== | ==2xml - KDM4C catalytic domain== | ||
'''2xml''' is a 2 chain structure. This domain belongs to the [https://en.wikipedia.org/wiki/Human Human] | '''2xml''' is a 2 chain structure. This domain belongs to the [https://en.wikipedia.org/wiki/Human Human] KDM4C protein. | ||
[https://en.wikipedia.org/wiki/KDM4C KDM4C] is a '''histone demethylase''' involved in the specific demethylation of trimethylated residues (Lys 9 and Lys 36 of histone 3). | [https://en.wikipedia.org/wiki/KDM4C KDM4C] is a '''histone demethylase''' involved in the specific demethylation of trimethylated residues (Lys 9 and Lys 36 of histone 3). | ||
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'''Genes expression''' is directly related to the '''condensation state''' of the [https://en.wikipedia.org/wiki/Chromatin chromatin]. Indeed, chromatin can be in the form of [https://en.wikipedia.org/wiki/Heterochromatin heterochromatin] (condensed form of DNA) or [https://en.wikipedia.org/wiki/Euchromatin euchromatin] (relaxed form of DNA) which correspond respectively to the transcriptionally silent and active forms of DNA. Chromatin is composed of DNA wrapped around [https://en.wikipedia.org/wiki/Histone histone] octamers forming nucleosomes<ref>Tamaru, H. “Confining Euchromatin/Heterochromatin Territory: Jumonji Crosses the Line.” Genes & Development 24, no. 14 (July 15, 2010): 1465–78. https://doi.org/10.1101/gad.1941010.</ref>. | '''Genes expression''' is directly related to the '''condensation state''' of the [https://en.wikipedia.org/wiki/Chromatin chromatin]. Indeed, chromatin can be in the form of [https://en.wikipedia.org/wiki/Heterochromatin heterochromatin] (condensed form of DNA) or [https://en.wikipedia.org/wiki/Euchromatin euchromatin] (relaxed form of DNA) which correspond respectively to the transcriptionally silent and active forms of DNA. Chromatin is composed of DNA wrapped around [https://en.wikipedia.org/wiki/Histone histone] octamers forming nucleosomes<ref>Tamaru, H. “Confining Euchromatin/Heterochromatin Territory: Jumonji Crosses the Line.” Genes & Development 24, no. 14 (July 15, 2010): 1465–78. https://doi.org/10.1101/gad.1941010.</ref>. | ||
The '''histone tails residues''' can be [https://en.wikipedia.org/wiki/Acetylation acetylated], [https://en.wikipedia.org/wiki/Methylation methylated] or [https://en.wikipedia.org/wiki/Demethylation demethylated] by enzymes in order to modify chromatin state and therefore gene expression. Different types of proteins involved in this process exist, such as histone | The '''histone tails residues''' can be [https://en.wikipedia.org/wiki/Acetylation acetylated], [https://en.wikipedia.org/wiki/Methylation methylated] or [https://en.wikipedia.org/wiki/Demethylation demethylated] by enzymes in order to modify chromatin state and therefore gene expression. Different types of proteins involved in this process exist, such as histone acetyltransferase (HAT), histone methyltransferase (HMT) or histone demethylase (HDM)<ref>Nasir Javaid, and Sangdun Choi. “Acetylation- and Methylation-Related Epigenetic Proteins in the Context of Their Targets.” Genes 8, no. 8 (August 7, 2017): 196. https://doi.org/10.3390/genes8080196</ref>. | ||
Two families of [https://en.wikipedia.org/wiki/Demethylase histone-lysine demethylase] (KDM) have been identified as follows : the '''flavin (FAD)-dependent lysine-specific demethylases''' and the '''Fe(II)-dependent Jumonji C (JmjC) family'''. JmjC is subfamily of histone demethylases which regroups several proteins containing a specific catalytic domain called '''Jmjc''' found in ''' 2xml structure'''<ref>Shi, Y. G., and Y.-i. Tsukada. “The Discovery of Histone Demethylases.” Cold Spring Harbor Perspectives in Biology 5, no. 9 (September 1, 2013): a017947–a017947. https://doi.org/10.1101/cshperspect.a017947.</ref>. KDM4 demethylases belong to the JmjC family and contains six members : KDM4A-F<ref>Labbé, Roselyne M., Andreana Holowatyj, and Zeng-Quan Yang. “Histone Lysine Demethylase (KDM) Subfamily 4: Structures, Functions and Therapeutic Potential.” American Journal of Translational Research 6, no. 1 (2013): 1–15</ref>. | Two families of [https://en.wikipedia.org/wiki/Demethylase histone-lysine demethylase] (KDM) have been identified as follows : the '''flavin (FAD)-dependent lysine-specific demethylases''' and the '''Fe(II)-dependent Jumonji C (JmjC) family'''. JmjC is subfamily of histone demethylases which regroups several proteins containing a specific catalytic domain called '''Jmjc''' found in ''' 2xml structure'''<ref>Shi, Y. G., and Y.-i. Tsukada. “The Discovery of Histone Demethylases.” Cold Spring Harbor Perspectives in Biology 5, no. 9 (September 1, 2013): a017947–a017947. https://doi.org/10.1101/cshperspect.a017947.</ref>. KDM4 demethylases belong to the JmjC family and contains six members : KDM4A-F<ref>Labbé, Roselyne M., Andreana Holowatyj, and Zeng-Quan Yang. “Histone Lysine Demethylase (KDM) Subfamily 4: Structures, Functions and Therapeutic Potential.” American Journal of Translational Research 6, no. 1 (2013): 1–15</ref>. | ||
[[Image:Reactionjpg.jpg | thumb | | [[Image:Reactionjpg.jpg | thumb | upright=3,5 | Enzymatic reaction of demethylation of H3K9(me3) and H3K36(me3) by KDM4C ]] | ||
'''KDM4C/JMJD2''' is a protein which converts specifically trimethylated histone residues to the dimethylated form. Indeed, it catalyzes the demethylation of both '''Lysine 9 and Lysine 36 of histone 3''' (respectively H3K9me3 and H3K36me3 by hydroxylation of the lysine methyl group. This reaction leads to a dissociation of the methyl group from the lysine histone tail. KDM4C employs [https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid 2-oxoglutarate] (OG), Fe2+ and oxygen as cosubstrates to promote its enzymatic reaction, thus the '''dissociation of one methyl group'''<ref>Leurs, Ulrike, Brian Lohse, Kasper D. Rand, Shonoi Ming, Erik S. Riise, Philip A. Cole, Jesper L. Kristensen, and Rasmus P. Clausen. “Substrate- and Cofactor-Independent Inhibition of Histone Demethylase KDM4C.” ACS Chemical Biology 9, no. 9 (September 19, 2014): 2131–38. https://doi.org/10.1021/cb500374f.</ref>. | '''KDM4C/JMJD2''' is a protein which converts specifically trimethylated histone residues to the dimethylated form. Indeed, it catalyzes the demethylation of both '''Lysine 9 and Lysine 36 of histone 3''' (respectively H3K9me3 and H3K36me3 by hydroxylation of the lysine methyl group. This reaction leads to a dissociation of the methyl group from the lysine histone tail. KDM4C employs [https://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid 2-oxoglutarate] (OG), Fe2+ and oxygen as cosubstrates to promote its enzymatic reaction, thus the '''dissociation of one methyl group'''<ref>Leurs, Ulrike, Brian Lohse, Kasper D. Rand, Shonoi Ming, Erik S. Riise, Philip A. Cole, Jesper L. Kristensen, and Rasmus P. Clausen. “Substrate- and Cofactor-Independent Inhibition of Histone Demethylase KDM4C.” ACS Chemical Biology 9, no. 9 (September 19, 2014): 2131–38. https://doi.org/10.1021/cb500374f.</ref>. | ||
