2014
DOI: 10.4161/cc.28104
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The histone methyltransferase Dot1/DOT1L as a critical regulator of the cell cycle

Abstract: Dot1/DOT1L catalyzes the methylation of histone H3 lysine 79 (H3K79), which regulates diverse cellular processes, such as development, reprogramming, differentiation, and proliferation. In regards to these processes, studies of Dot1/DOT1L-dependent H3K79 methylation have mainly focused on the transcriptional regulation of specific genes. Although the gene transcription mediated by Dot1/DOT1L during the cell cycle is not fully understood, H3K79 methylation plays a critical role in the progression of G1 phase, S… Show more

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Cited by 99 publications
(88 citation statements)
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References 122 publications
(292 reference statements)
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“…The myeloid cell line KG1 and its subline KG1a, as well as the T-ALL cell line Loucy, all express HOXA9 at a level similar or observed in several HOXA9 -samples, including those with inv(16) (Supplemental Figure 8, B and C). Correlation with cytogenetics revealed that 3 samples with high MN1/HOXA9 expression had a complex karyotype with loss of 5q and/or 7q sequences (AML 38,19,and 40). On the other hand, we found that 6 of 12 AML samples with high MN1 expression had no detectable HOXA9/MEIS1 expression.…”
Section: Discussionmentioning
confidence: 57%
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“…The myeloid cell line KG1 and its subline KG1a, as well as the T-ALL cell line Loucy, all express HOXA9 at a level similar or observed in several HOXA9 -samples, including those with inv(16) (Supplemental Figure 8, B and C). Correlation with cytogenetics revealed that 3 samples with high MN1/HOXA9 expression had a complex karyotype with loss of 5q and/or 7q sequences (AML 38,19,and 40). On the other hand, we found that 6 of 12 AML samples with high MN1 expression had no detectable HOXA9/MEIS1 expression.…”
Section: Discussionmentioning
confidence: 57%
“…This is consistent with the observed phenotypic effects on growth and cell cycle. H3K79 methylation has been associated with cell cycle regulation in several experimental systems (40,41). It is thus possible that the observed decrease in cell cycle regulatory programs is a direct consequence of the loss of H3K79 methylation.…”
Section: Methodsmentioning
confidence: 99%
“…Another example is that H3K79me1/2/3s were all asymmetrically distributed on the old H3 in mitosis ( Table 1), suggesting that the sole methyltransferase for H3K79, Dot1l (31), was preferentially recruited to old histone H3. Interestingly, Dot1/Dot1l deficiency causes various cell cycle defects in human cells and in other organisms (32), which might be related to its enrichment on the old H3. In addition, although K27me2 was asymmetrically distributed on the old histone H3.1/2, its counterpart was symmetrically distributed on H3.3.…”
Section: Systematic Analysis Of the Distribution Of Histone Ptms Inmentioning
confidence: 99%
“…Peptide sequences that were not analyzed in this study are in gray. The H3.1/2(27-40) peptide is in blue, and the H3.3 (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) peptide is in red. The line connecting the four acetylation marks on H4(2-16) peptide indicates only the four-ac was enriched on old H4 but not two-ac or three-ac (Table 1).…”
Section: Mass Spectrometry Provides a Powerful Tool To Study Dynamicsmentioning
confidence: 99%
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