scholarly journals KDM5B protein expressed in viable and fertile ΔARID mice exhibit no demethylase activity

2021 ◽  
Vol 59 (5) ◽  
Author(s):  
Shirin Jamshidi ◽  
Steven Catchpole ◽  
Jie Chen ◽  
Chi So ◽  
Joy Burchell ◽  
...  
Keyword(s):  
Demethylase Activity

scholarly journals Effect of Posttranslational Modifications on the Structure and Activity of FTO Demethylase

2021 ◽  
Vol 22 (9) ◽  
pp. 4512
Author(s):  
Michał Marcinkowski ◽  
Tomaš Pilžys ◽  
Damian Garbicz ◽  
Jan Piwowarski ◽  
Damian Mielecki ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Size Exclusion Chromatography ◽  
Posttranslational Modifications ◽  
Size Exclusion ◽  
Saxs Data ◽  
Wide Range ◽  
Exclusion Chromatography ◽  
Demethylase Activity ◽  
Structure And Activity

The FTO protein is involved in a wide range of physiological processes, including adipogenesis and osteogenesis. This two-domain protein belongs to the AlkB family of 2-oxoglutarate (2-OG)- and Fe(II)-dependent dioxygenases, displaying N6-methyladenosine (N6-meA) demethylase activity. The aim of the study was to characterize the relationships between the structure and activity of FTO. The effect of cofactors (Fe2+/Mn2+ and 2-OG), Ca2+ that do not bind at the catalytic site, and protein concentration on FTO properties expressed in either E. coli (ECFTO) or baculovirus (BESFTO) system were determined using biophysical methods (DSF, MST, SAXS) and biochemical techniques (size-exclusion chromatography, enzymatic assay). We found that BESFTO carries three phosphoserines (S184, S256, S260), while there were no such modifications in ECFTO. The S256D mutation mimicking the S256 phosphorylation moderately decreased FTO catalytic activity. In the presence of Ca2+, a slight stabilization of the FTO structure was observed, accompanied by a decrease in catalytic activity. Size exclusion chromatography and MST data confirmed the ability of FTO from both expression systems to form homodimers. The MST-determined dissociation constant of the FTO homodimer was consistent with their in vivo formation in human cells. Finally, a low-resolution structure of the FTO homodimer was built based on SAXS data.

scholarly journals A mammalian mutant cell lacking detectable lanosterol 14 alpha-methyl demethylase activity.

1988 ◽  
Vol 263 (3) ◽  
pp. 1248-1254
Author(s):  
H W Chen ◽  
D A Leonard ◽  
R T Fischer ◽  
J M Trzaskos
Keyword(s):  
Mutant Cell ◽  
Demethylase Activity

scholarly journals Demethylase Activity Is Directed by Histone Acetylation

2001 ◽  
Vol 276 (44) ◽  
pp. 40778-40787 ◽  
Author(s):  
Nadia Cervoni ◽  
Moshe Szyf
Keyword(s):  
Histone Acetylation ◽  
Demethylase Activity

scholarly journals Whole Genome Sequencing Reveals the Effects of Recent Artificial Selection on Litter Size of Bamei Mutton Sheep

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 157
Author(s):  
Yaxin Yao ◽  
Zhangyuan Pan ◽  
Ran Di ◽  
Qiuyue Liu ◽  
Wenping Hu ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Litter Size ◽  
Artificial Selection ◽  
Estrogen Signaling ◽  
Meat Production ◽  
Domestic Sheep ◽  
Whole Genome ◽  
Nonsynonymous Mutation ◽  
Demethylase Activity ◽  
Mongolian Sheep

Bamei mutton sheep is a Chinese domestic sheep breed developed by crossing German Mutton Merino sheep and indigenous Mongolian sheep for meat production. Here, we focused on detecting candidate genes associated with the increasing of the litter size in this breeds under recent artificial selection to improve the efficiency of mutton production. We selected five high- and five low-fecundity Bamei mutton sheep for whole-genome resequencing to identify candidate genes for sheep prolificacy. We used the FST and XP-EHH statistical approach to detect the selective sweeps between these two groups. Combining the two selective sweep methods, the reproduction-related genes JUN, ITPR3, PLCB2, HERC5, and KDM4B were detected. JUN, ITPR3, and PLCB2 play vital roles in GnRH (gonadotropin-releasing hormone), oxytocin, and estrogen signaling pathway. Moreover, KDM4B, which had the highest FST value, exhibits demethylase activity. It can affect reproduction by binding the promoters of estrogen-regulated genes, such as FOXA1 (forkhead box A1) and ESR1 (estrogen receptor 1). Notably, one nonsynonymous mutation (p.S936A) specific to the high-prolificacy group was identified at the TUDOR domain of KDM4B. These observations provide a new opportunity to research the genetic variation influencing fecundity traits within a population evolving under artificial selection. The identified genomic regions that are responsible for litter size can in turn be used for further selection.

scholarly journals LSD1/KDM1A mutations associated to a newly described form of intellectual disability impair demethylase activity and binding to transcription factors

2016 ◽  
pp. ddw120 ◽  
Author(s):  
Simona Pilotto ◽  
Valentina Speranzini ◽  
Chiara Marabelli ◽  
Francesco Rusconi ◽  
Emanuela Toffolo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Intellectual Disability ◽  
Demethylase Activity

scholarly journals KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance

Cancer Cell ◽  
2019 ◽  
Vol 35 (2) ◽  
pp. 330-332 ◽  
Author(s):  
Kunihiko Hinohara ◽  
Hua-Jun Wu ◽  
Sébastien Vigneau ◽  
Thomas O. McDonald ◽  
Kyomi J. Igarashi ◽  
...  
Keyword(s):  
Histone Demethylase ◽  
Therapeutic Resistance ◽  
Demethylase Activity

Modular arrangements of sequence motifs determine the functional diversity of KDM proteins

2020 ◽  
Author(s):  
Zerong Wang ◽  
Dongyang Liu ◽  
Baofang Xu ◽  
Ruixia Tian ◽  
Yongchun Zuo
Keyword(s):  
Vital Role ◽  
Sequence Motifs ◽  
Chromatin Dynamics ◽  
Regulatory Motifs ◽  
Demethylase Activity ◽  
Functional Features ◽  
Catalytic Motif ◽  
Functional Mechanisms ◽  
Deep Exploration ◽  
First Time

Abstract Histone lysine demethylases (KDMs) play a vital role in regulating chromatin dynamics and transcription. KDM proteins are given modular activities by its sequence motifs with obvious roles division, which endow the complex and diverse functions. In our review, according to functional features, we classify sequence motifs into four classes: catalytic motifs, targeting motifs, regulatory motifs and potential motifs. JmjC, as the main catalytic motif, combines to Fe2+ and α-ketoglutarate by residues H-D/E-H and S-N-N/Y-K-N/Y-T/S. Targeting motifs make catalytic motifs recognize specific methylated lysines, such as PHD that helps KDM5 to demethylate H3K4me3. Regulatory motifs consist of a functional network. For example, NLS, Ser-rich, TPR and JmjN motifs regulate the nuclear localization. And interactions through the CW-type-C4H2C2-SWIRM are necessary to the demethylase activity of KDM1B. Additionally, many conservative domains that have potential functions but no deep exploration are reviewed for the first time. These conservative domains are usually amino acid-rich regions, which have great research value. The arrangements of four types of sequence motifs generate that KDM proteins diversify toward modular activities and biological functions. Finally, we draw a blueprint of functional mechanisms to discuss the modular activity of KDMs.

scholarly journals The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance

Blood ◽  
2019 ◽  
Vol 134 (14) ◽  
pp. 1154-1158 ◽  
Author(s):  
Karl Agger ◽  
Koutarou Nishimura ◽  
Satoru Miyagi ◽  
Jan-Erik Messling ◽  
Kasper Dindler Rasmussen ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Clinical Use ◽  
Histone Demethylases ◽  
Hematopoietic Stem ◽  
Stem Cell Maintenance ◽  
Demethylase Activity ◽  
Cell Maintenance ◽  
Acute Myeloid

Abstract KDM4 and JMJD2 are histone demethylases that are considered promising targets for treatment of MLL translocation–bearing acute myeloid leukemia. Agger and colleagues demonstrate an important role of KDM4 activity in long-term normal hematopoiesis that should be considered when contemplating the clinical use of long-term inhibition of KDM4 demethylase activity.

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