KRAB-ZFP binds retroelement DNA in chromatin

Stable Identifier
R-HSA-9842835
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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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

Shinkai, Y, Okada, Y, Kaneko, S, Fukuda, K, Makino, Y, Ichiyanagi, K, Shimura, C

Elife 2022
25274305 An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons

Katzman, S, Haeussler, M, Salama, SR, Haussler, D, Paten, B, Nguyen, N, Greenberg, D, Ewing, AD, Jacobs, FM

Nature 2014
37730438 Genetic features and genomic targets of human KRAB-zinc finger proteins

Khubieh, B, Fellay, J, Imbeault, M, Turelli, P, Duc, J, Offner, S, de Tribolet-Hardy, J, Forey, R, Pulver, C, Thorball, CW, Planet, E, Coudray, A, Trono, D

Genome Res 2023
31006620 Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs

Duc, J, Turelli, P, Offner, S, Pontis, J, Jaenisch, R, Planet, E, Coudray, A, Trono, D, Theunissen, TW

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

Chobirko, JD, Feschotte, C, Dumbović, G, Rinn, JL, Singh, M, Carter, TA

Elife 2022
25690854 C2H2 zinc finger proteins greatly expand the human regulatory lexicon

Greenblatt, J, Kim, PM, Mnaimneh, S, Albu, M, Weirauch, MT, Frey, BJ, Schmitges, FW, Radovani, E, Yang, A, Hughes, TR, Garton, M, Najafabadi, HS, Lam, KN

Nat Biotechnol 2015
27852650 Multiparameter functional diversity of human C2H2 zinc finger proteins

Zhong, G, Yin, Y, Campitelli, LF, Greenblatt, JF, Guo, H, Dai, WF, Schmitges, FW, Radovani, E, Emili, A, Hughes, TR, Taipale, J, Jolma, A, Najafabadi, HS, Barazandeh, M, Kanagalingam, T

Genome Res 2016
28273063 KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks

Trono, D, Helleboid, PY, Imbeault, M

Nature 2017
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