Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters

Petkau, Nikolai; Budak, Harun; Zhou, Xunlei; Oster, Henrik; Eichele, Gregor

doi:10.7554/elife.43235

Cited by 29 publications

(32 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, a primary target of TIP60 histone acetylation, histone H4, is not rhythmically acetylated at the per and tim loci in Drosophila 66 , but whether acetylation of TIP60 targets H2A and H2Az is rhythmic at these clock genes is not known. In mice, TIP60 acetylates BMAL1 (ortholog of Drosophila CYC) at K538 to promote CLOCK-BMAL1 transcription elongation 67 , but since CYC lacks the C-terminal region that would contain K538 such regulation can’t occur in Drosophila. Our results show that Tip60 enhances the power of behavioral rhythms, presumably by maintaining the amplitude of molecular rhythms.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A

Mahesh

Rivas

Caster

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Circadian clocks keep time via ~ 24 h transcriptional feedback loops. In Drosophila, CLOCK-CYCLE (CLK-CYC) activators and PERIOD-TIMELESS (PER-TIM) repressors are feedback loop components whose transcriptional status varies over a circadian cycle. Although changes in the state of activators and repressors has been characterized, how their status is translated to transcriptional activity is not understood. We used mass spectrometry to identify proteins that interact with GFP-tagged CLK (GFP-CLK) in fly heads at different times of day. Many expected and novel interacting proteins were detected, of which several interacted rhythmically and were potential regulators of protein levels, activity or transcriptional output. Genes encoding these proteins were tested to determine if they altered circadian behavior via RNAi knockdown in clock cells. The NIPPED-A protein, a scaffold for the SAGA and Tip60 histone modifying complexes, interacts with GFP-CLK as transcription is activated, and reducing Nipped-A expression lengthens circadian period. RNAi analysis of other SAGA complex components shows that the SAGA histone deubiquitination (DUB) module lengthened period similarly to Nipped-A RNAi knockdown and weakened rhythmicity, whereas reducing Tip60 HAT expression drastically weakened rhythmicity. These results suggest that CLK-CYC binds NIPPED-A early in the day to promote transcription through SAGA DUB and Tip60 HAT activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A

Mahesh

Rivas

Caster

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Recently, Tip60 protein was identified as the acetyltransferase of Bmal1. Tip60 protein catalyzed the K538 acetylation of BMAL1 and activated BMAL1 ( Petkau et al, 2019 ). Tip60 protein could be phosphorylated on S86 by GSK3b to activate its acetyltransferase activity ( Lin et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

A Sextuple Knockout Cell Line System to Study the Differential Roles of CRY, PER, and NR1D in the Transcription-Translation Feedback Loop of the Circadian Clock

Chiou

Yang

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

The transcription-translation feedback loop (TTFL) is the core mechanism of the circadian rhythm. In mammalian cells, CLOCK-BMAL1 proteins activate the downstream genes by binding on the E-box sequence of the clock-controlled genes. Among these gene products, CRY1, CRY2, PER1, PER2, NR1D1, and NR1D2 can regulate the CLOCK-BMAL1-mediated transcription to form the feedback loop. However, the detailed mechanism of the TTFL is unclear because of the complicated inter-regulation of these proteins. Here, we generated a cell line lacking CRY1, CRY2, PER1, PER2, NR1D1, and NR1D2 (Cry/Per/Nr1d_KO) to study TTFL. We compared the Dbp transcription after serum-shock and dexamethasone-shock between Cry/Per/Nr1d_KO cells and cells expressing endogenous CRY (Per/Nr1d_KO) or NR1D (Cry/Per_KO). Furthermore, we found that CRY1-mediated repression of Dbp could persist more than 24 h in the absence of other proteins in the negative limb of the TTFL. Our Cry/Per/Nr1d_KO cells is a suitable system for the studying of differential roles of CRY, PER, and NR1D in the TTFL.

show abstract

“…To generate liver-speci c Tip60 knockout mice (mutant), Tip60 oxed mice (10)(11)(12) week old male) with loxP sites anking exons 1 and 9 of the Tip60 gene [21] were crossed to a SACre driver mouse line resulting in Cre-mediated deletion of Tip60 in the liver [26]. Mice were previously backcrossed to a C57BL/6N background for at least 10 generations.…”

Section: Liver-speci C Conditional Knockout Mouse Modelmentioning

confidence: 99%

“…Genotyping was performed with gene-speci c primers [21,26]. Liver and kidney tissues were collected ve days after the last injection.…”

Section: Liver-speci C Conditional Knockout Mouse Modelmentioning

confidence: 99%

Tip60 Might Be a Candidate For The Acetylation of Hepatic Carbonic Anhydrase I and III in Mice

BALTACI

Koçpınar

Budak

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Carbonic anhydrases (CAs) play an important role in maintaining pH balance by catalyzing the conversion of carbon dioxide to bicarbonate. Since this pH balance is critical to health, all organisms must develop mechanisms to control and regulate it. Although there is a great deal of literature on the biochemical, functional, and structural properties of the CA family, there is no enough knowledge on the regulation of CAs at gene and protein levels, especially their epigenetic regulation. In this study, impact of Tip60, a member of histone acetyltransferases family, on the expression of Ca1 and Ca3 genes in liver tissue was investigated at different zeitgeber time points in control and liver-specific Tip60 knockout mice (mutant) groups. First of all, Tip60 was specifically knocked out in mouse liver the using Cre/loxP system and knockout rate was shown as 83% - 88% by southern blot. Expression profiles of Ca1 and Ca3 genes in both groups were determined by Real-Time PCR at six different time points. While Ca1 showed the highest expression at ZT8 and ZT12, the lowest expression profile was observed at ZT0 and ZT20. Hepatic Ca1 showed a robust circadian expression. While hepatic Ca3 showed almost the same level of expression at different time units. The expression of Ca1 and Ca3 significantly decreased in the absence of Tip60 in mouse liver all time period. In conclusion, it was suggested for the first time that Tip60 may be considered a candidate protein in the regulation of Ca1 and Ca3 genes, possibly by acetylation.

show abstract

Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters

Cited by 29 publications

References 70 publications

Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A

Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A

A Sextuple Knockout Cell Line System to Study the Differential Roles of CRY, PER, and NR1D in the Transcription-Translation Feedback Loop of the Circadian Clock

Tip60 Might Be a Candidate For The Acetylation of Hepatic Carbonic Anhydrase I and III in Mice

Contact Info

Product

Resources

About