Reactome | KRAB-ZFP binds retroelement DNA in chromatin

KRAB-ZFP binds retroelement DNA in chromatin

Stable Identifier

R-HSA-9842835

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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KRAB-ZFP binds retroelement DNA in chromatin

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The C-terminal zinc finger domains of KRAB-ZFPs bind particular DNA sequences (Jacobs et al. 2014, Najafabadi et al. 2015, Schmitges et al. 2016, Imbeault et al. 2017, Carter et al. 2022, Fukuda et al. 2022, meta-analysis of bound motifs in Barazandeh et al. 2018). Amino acid residues 1, 2, 3, and 6 of the C2H2 α-helix are responsible for the direct interactions with specific DNA target sites (Pavletich and Pabo 1991). Systematic chromatin immunoprecipitations demonstrate that about two thirds or more of KRAB-ZFPs bind sequences in retroelements, with each specific KRAB-ZFP binding a specific set of retroelements (Najafabadi et al. 2015, Schmitges et al. 2016, Imbeault et al. 2017, de Tribolet-Hardy et al. 2023). Some KRAB-ZFPs such as ZNF91 and ZNF93 appear to evolve in response to the appearance of new retroelements and repress the transcription of these retrolements until new derivatives of the retroelement appear that have lost the binding site for the KRAB-ZFP (Jacobs et al. 2014). In humans, evolutionarily young retroelements are transcribed in the 4-cell to morula stages during embryogenesis and serve as enhancers for expression of neighboring genes until silenced by KRAB-ZFPs (Pontis et al. 2019, Carter et al. 2022).

Literature References

PubMed ID	Title	Journal	Year
35315771	Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells Fukuda, K, Makino, Y, Kaneko, S, Shimura, C, Okada, Y, Ichiyanagi, K, Shinkai, Y	Elife	2022
25274305	An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons Jacobs, FM, Greenberg, D, Nguyen, N, Haeussler, M, Ewing, AD, Katzman, S, Paten, B, Salama, SR, Haussler, D	Nature	2014
37730438	Genetic features and genomic targets of human KRAB-zinc finger proteins de Tribolet-Hardy, J, Thorball, CW, Forey, R, Planet, E, Duc, J, Coudray, A, Khubieh, B, Offner, S, Pulver, C, Fellay, J, Imbeault, M, Turelli, P, Trono, D	Genome Res	2023
31006620	Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs Pontis, J, Planet, E, Offner, S, Turelli, P, Duc, J, Coudray, A, Theunissen, TW, Jaenisch, R, Trono, D	Cell Stem Cell	2019
2028256	Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A Pavletich, NP, Pabo, CO	Science	1991
35179489	Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo Carter, TA, Singh, M, Dumbović, G, Chobirko, JD, Rinn, JL, Feschotte, C	Elife	2022
25690854	C2H2 zinc finger proteins greatly expand the human regulatory lexicon Najafabadi, HS, Mnaimneh, S, Schmitges, FW, Garton, M, Lam, KN, Yang, A, Albu, M, Weirauch, MT, Radovani, E, Kim, PM, Greenblatt, J, Frey, BJ, Hughes, TR	Nat Biotechnol	2015
27852650	Multiparameter functional diversity of human C2H2 zinc finger proteins Schmitges, FW, Radovani, E, Najafabadi, HS, Barazandeh, M, Campitelli, LF, Yin, Y, Jolma, A, Zhong, G, Guo, H, Kanagalingam, T, Dai, WF, Taipale, J, Emili, A, Greenblatt, JF, Hughes, TR	Genome Res	2016
28273063	KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks Imbeault, M, Helleboid, PY, Trono, D	Nature	2017