A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

Altemose, Nicolas and Noor, Nudrat and Bitoun, Emmanuelle and Tumian, Afidalina and Imbeault, Michaël and Chapman, J. Ross and Aricescu, A. Radu and Myers, Simon R. (2017) A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis. eLife, 6. pp. 1-46. E-ISSN 2050-084X

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Abstract

PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.

Item Type:	Article (Journal)
Additional Information:	4915/59029
Uncontrolled Keywords:	human PRDM9 map, PRDM9, zinc-finger proteins, meiosis
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Information and Communication Technology > Department of Computer Science Kulliyyah of Information and Communication Technology > Department of Computer Science
Depositing User:	Dr Afidalina Tumian
Date Deposited:	03 Nov 2017 11:48
Last Modified:	28 Mar 2018 09:02
URI:	http://irep.iium.edu.my/id/eprint/59029

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