A highly basic histone H4 domain bound to the sharply bent region of nucleosomal DNA

Konstantin K. Ebralidse; Sergei A. Grachev; Andrei D. Mirzabekov

doi:10.1038/331365a0

Chromatin Condensation Fluctuations Rather than Steady-State Predict Chromatin Accessibility

10.1101/365700 ◽

2018 ◽

Cited By ~ 1

Author(s):

Nicolas Audugé ◽

Sergi Padilla-Parra ◽

Marc Tramier ◽

Nicolas Borghi ◽

Maïté Coppey-Moisan

Keyword(s):

Cell Biology ◽

Dynamic Properties ◽

Chromatin Condensation ◽

Direct Interaction ◽

Chromatin Accessibility ◽

Live Cells ◽

Histone H4 ◽

Epigenetic Marks ◽

Nucleosomal Dna ◽

Acetylated Histone H4

AbstractChromatin accessibility to protein factors is critical for genome activities. Dynamic changes in nucleosomal DNA compaction and higher order chromatin structures are expected to allow specific sites to be accessible to regulatory factors and the transcriptional machinery. However, the dynamic properties of chromatin that regulate its accessibility are poorly understood. Here, we took advantage of the microenvironment sensitivity of the fluorescence lifetime of EGFP-H4 histone incorporated in chromatin to map in the nucleus of live cells the dynamics of chromatin condensation and its direct interaction with a tail acetylation recognition domain (the double bromodomain module of human TAFII250, dBD). We reveal chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation. Fluctuations are spontaneous, yet their amplitudes are affected by their sub-nuclear localization and by distinct and competing mechanisms dependent on histone acetylation, ATP, and both. Moreover, we show that accessibility of acetylated histone H4 to dBD is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.SignificanceIn higher eukaryotes, the structure and compaction of chromatin are considered as barriers to genome activities. Epigenetic marks such as post-translational modifications of histones can modify the structure and compaction of chromatin. The accessibility of protein factors to these epigenetic marks is therefore of paramount importance for genome activities. We reveal chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation itself. We show that accessibility of acetylated histone H4 to double bromodomains is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.ClassificationBiological Sciences, Cell Biology

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Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro.

The EMBO Journal ◽

10.1002/j.1460-2075.1996.tb00608.x ◽

1996 ◽

Vol 15 (10) ◽

pp. 2508-2518 ◽

Cited By ~ 299

Author(s):

M. Vettese-Dadey ◽

P. A. Grant ◽

T. R. Hebbes ◽

C. Crane- Robinson ◽

C. D. Allis ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factor Binding ◽

Primary Role ◽

Histone H4 ◽

Factor Binding ◽

Nucleosomal Dna

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Semisynthesis of site-specifically succinylated histone reveals that succinylation regulates nucleosome unwrapping rate and DNA accessibility

Nucleic Acids Research ◽

10.1093/nar/gkaa663 ◽

2020 ◽

Vol 48 (17) ◽

pp. 9538-9549

Author(s):

Yihang Jing ◽

Dongbo Ding ◽

Gaofei Tian ◽

Ka Chun Jonathan Kwan ◽

Zheng Liu ◽

...

Keyword(s):

Dna Damage ◽

Posttranslational Modifications ◽

Dna Damage Repair ◽

Histone H4 ◽

Chromatin Dynamics ◽

Nucleosome Dynamics ◽

Nucleosomal Dna ◽

Damage Repair

Abstract Posttranslational modifications (PTMs) of histones represent a crucial regulatory mechanism of nucleosome and chromatin dynamics in various of DNA-based cellular processes, such as replication, transcription and DNA damage repair. Lysine succinylation (Ksucc) is a newly identified histone PTM, but its regulation and function in chromatin remain poorly understood. Here, we utilized an expressed protein ligation (EPL) strategy to synthesize histone H4 with site-specific succinylation at K77 residue (H4K77succ), an evolutionarily conserved succinylation site at the nucleosomal DNA-histone interface. We then assembled mononucleosomes with the semisynthetic H4K77succ in vitro. We demonstrated that this succinylation impacts nucleosome dynamics and promotes DNA unwrapping from the histone surface, which allows proteins such as transcription factors to rapidly access buried regions of the nucleosomal DNA. In budding yeast, a lysine-to-glutamic acid mutation, which mimics Ksucc, at the H4K77 site reduced nucleosome stability and led to defects in DNA damage repair and telomere silencing in vivo. Our findings revealed this uncharacterized histone modification has important roles in nucleosome and chromatin dynamics.

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Cryo-EM structure of the human Mixed Lineage Leukemia-1 complex bound to the nucleosome

10.1101/737478 ◽

2019 ◽

Author(s):

Sang Ho Park ◽

Alex Ayoub ◽

Young Tae Lee ◽

Jing Xu ◽

Hanseong Kim ◽

...

Keyword(s):

Mixed Lineage Leukemia ◽

Chromatin Binding ◽

Histone H4 ◽

Core Complex ◽

Regulate Gene Expression ◽

Histone Methyltransferases ◽

Nucleosome Core ◽

Nucleosomal Dna ◽

Histone H3k4 ◽

Methylation Activity

SUMMARYMixed Lineage Leukemia (MLL) family histone methyltransferases are the key enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanism by which the MLL complexes recognize histone H3K4 within the nucleosome core particle (NCP) remains unclear. Here, we report the single-particle cryo-electron microscopy (cryo-EM) structure of the human MLL1 core complex bound to the NCP. The MLL1 core complex anchors on the NCP through RbBP5 and ASH2L, which interacts extensively with nucleosomal DNA as well as the surface close to histone H4 N-terminal tail. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1SET domain at the nucleosome dyad, allowing symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.

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Regulation of ISW2 by Concerted Action of Histone H4 Tail and Extranucleosomal DNA

Molecular and Cellular Biology ◽

10.1128/mcb.01159-06 ◽

2006 ◽

Vol 26 (20) ◽

pp. 7388-7396 ◽

Cited By ~ 62

Author(s):

Weiwei Dang ◽

Mohamedi N. Kagalwala ◽

Blaine Bartholomew

Keyword(s):

Incubation Time ◽

Photoaffinity Labeling ◽

Histone H4 ◽

Concerted Action ◽

Optimal Length ◽

Nucleosome Remodeling ◽

Dna Footprinting ◽

Nucleosomal Dna ◽

Histone Octamers

ABSTRACT The stable contact of ISW2 with nucleosomal DNA ∼20 bp from the dyad was shown by DNA footprinting and photoaffinity labeling using recombinant histone octamers to require the histone H4 N-terminal tail. Efficient ISW2 remodeling also required the H4 N-terminal tail, although the lack of the H4 tail can be mostly compensated for by increasing the incubation time or concentration of ISW2. Similarly, the length of extranucleosomal DNA affected the stable contact of ISW2 with this same internal nucleosomal site, with the optimal length being 70 to 85 bp. These data indicate the histone H4 tail, in concert with a favorable length of extranucleosomal DNA, recruits and properly orients ISW2 onto the nucleosome for efficient nucleosome remodeling. One consequence of this property of ISW2 is likely its previously observed nucleosome spacing activity.

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Cryo-EM structure of the human MLL1 core complex bound to the nucleosome

Nature Communications ◽

10.1038/s41467-019-13550-2 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 11

Author(s):

Sang Ho Park ◽

Alex Ayoub ◽

Young-Tae Lee ◽

Jing Xu ◽

Hanseong Kim ◽

...

Keyword(s):

Molecular Mechanisms ◽

Histone H4 ◽

Core Complex ◽

Regulate Gene Expression ◽

Histone Methyltransferases ◽

Nucleosome Core ◽

Nucleosome Core Particles ◽

Nucleosomal Dna ◽

Histone H3k4 ◽

Methylation Activity

AbstractMixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanisms whereby the MLL complexes recognize histone H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved RbBP5 and ASH2L, which interact extensively with nucleosomal DNA and the surface close to the N-terminal tail of histone H4. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1SET domain at the nucleosome dyad, thereby facilitating symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.

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