1. Histone Chaperones: Modulators of Chromatin Marks
Nikita Avvakumov, Amine Nourani, Jacques Côté 
Molecular Cell 
Volume 41, Issue 5, Pages (March 2011)
DOI: /j.molcel
Copyright © 2011 Elsevier Inc. Terms and Conditions

2. Figure 1 Activities of Histone Chaperones during DNA Replication
Only leading strand synthesis is shown for the sake of clarity. As the MCM helicase complex unwinds the DNA duplex ahead of the DNA polymerase, displaced histone dimers and tetramers are transferred to HCs, which then redeposit them on the newly replicated DNA behind the replication fork. Concomitantly, the same classes of chaperones are involved in the deposition of newly synthesized histones onto the replicated DNA. Following nucleosome reassembly, posttranslational modifications (PTMs) appropriate to the local chromatin structure are applied to the histones. This may involve inter- and/or intranucleosomal copying of PTMs from pre-existing onto new histones, as well as de novo PTM deposition, although the mechanisms responsible for either pathway are not yet known. Numbers within colored circles indicate histone residues subject to modification, as discussed in the main text.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2011 Elsevier Inc. Terms and Conditions

3. Figure 2
Roles Played by Histone Chaperones during Repair of DNA Double-Strand Breaks
Access: The variant histone H2AX is phosphorylated on S139 (S129 of H2A in S. cerevisiae) in the chromatin surrounding the site of damage. Once DNA resection commences, displaced histones are likely captured by chaperones. However, this has not been demonstrated, and identities of chaperones that may be involved in this process are unknown. Repair: While the repair machinery assembles and mends the break, PARP1, which is upregulated in response to damage, mediates poly-ADP-ribosylation of FACT, thereby rendering it inactive. Restore: With DNA damage repaired, HCs participate in restoration of the chromatin structure. Asf1/Rtt109 and CAF-1 deposit newly synthesized histones onto DNA to replace those lost during the repair process. Meanwhile, the FACT chaperone functions to exchange phosphorylated H2AX with an unmodified version in order to release any repair proteins retained by this mark and to permit resetting of the cell-cycle checkpoint triggered by damage.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2011 Elsevier Inc. Terms and Conditions

4. Figure 3 Involvement of Histone Chaperones in Transcription
Promoter: The two H2AZ-containing nucleosomes flanking the nucleosome-free region within the promoter are shown with bold outlines to indicate their relatively stable positioning. H3-H4 dimers displaced from the promoter are acetylated by Asf1/Rtt109 on Lys56 of H3 to facilitate their removal during subsequent cycles of transcription initiation. The precise mechanisms by which other HCs influence promoter activation are currently unknown. Coding region: Histones displaced by the advancing RNA polymerase are collected by the Spt6 and FACT HCs and redeposited onto transcribed DNA in its wake, while Asf1 and HIRA participate in the placement of newly synthesized histones H3.1 and H3.3. Nucleosome disassembly in front of the polymerase is facilitated by acetylation of histones by different candidate HAT complexes. The Spt6 chaperone promotes recruitment of the Set2 methyltransferase that methylates reassembled nucleosomes on Lys36 of H3. This mark is then used by the Rpd3S HDAC complex to remove histone acetylation (inset), thereby re-establishing a repressive chromatin structure that prevents inappropriate initiation of transcription from within the coding region.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2011 Elsevier Inc. Terms and Conditions