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Dynamic site-specific recruitment of RBP2 by pocket protein p130 modulates H3K4 methylation on E2F-responsive promoters
- Source :
- Nucleic Acids Research
- Publication Year :
- 2017
- Publisher :
- Oxford University Press, 2017.
-
Abstract
- The Histone 3 lysine 4 methylation (H3K4me3) mark closely correlates with active transcription. E2F-responsive promoters display dynamic changes in H3K4 methylation during the course of cell cycle progression. However, how and when these marks are reset, is not known. Here we show that the retinoblastoma binding protein RBP2/KDM5A, capable of removing tri-methylation marks on H3K4, associates with the E2F4 transcription factor via the pocket protein—p130—in a cell-cycle-stage specific manner. The association of RBP2 with p130 is LxCxE motif dependent. RNAi experiments reveal that p130 recruits RBP2 to E2F-responsive promoters in early G1 phase to bring about H3K4 demethylation and gene repression. A point mutation in LxCxE motif of RBP2 renders it incapable of p130-interaction and hence, repression of E2F-regulated gene promoters. We also examine how RBP2 may be recruited to non-E2F responsive promoters. Our studies provide insight into how the chromatin landscape needs to be adjusted rapidly and periodically during cell-cycle progression, concomitantly with temporal transcription, to bring about expression/repression of specific gene sets.
- Subjects :
- 0301 basic medicine
Amino Acid Motifs
E2F4 Transcription Factor
Biology
Methylation
Cell Line
Histones
03 medical and health sciences
Mice
Genetics
Animals
Humans
Amino Acid Sequence
E2F
Promoter Regions, Genetic
Transcription factor
Psychological repression
E2F4
Cells, Cultured
Retinoblastoma-Like Protein p130
Gene regulation, Chromatin and Epigenetics
G1 Phase
Promoter
Retinol-Binding Proteins, Cellular
Chromatin
Cell biology
E2F Transcription Factors
030104 developmental biology
Mutation
H3K4me3
RNA Interference
biological phenomena, cell phenomena, and immunity
Retinoblastoma-Binding Protein 2
HeLa Cells
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 13624962 and 03051048
- Volume :
- 46
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....ceb226e7e8db6d5defc1c18adc061c05