MIR sequences recruit zinc finger protein ZNF768 to expressed genes

Abstract

Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchromatin and promoter regions of genes. Binding was observed for genes expressed in a cell type-specific manner in human B cell line Raji and osteosarcoma U2OS cells. Mass spectrometric analysis revealed binding of ZNF768 to Elongator components Elp1, Elp2 and Elp3 and other nuclear factors. The N-terminus of ZNF768 contains a heptad repeat array structurally related to the C-terminal domain (CTD) of RNA polymerase II. This array evolved in placental animals but not marsupials and monotreme species, displays species-specific length variations, and possibly fulfills CTD related functions in gene regulation. We propose that the evolution of MIRs and ZNF768 has extended the repertoire of gene regulatory mechanisms in mammals and that ZNF768 binding is associated with cell type-specific gene expression.

Transposable elements as genetic accelerators of evolution: contribution to genome size, gene regulatory network rewiring and morphological innovation

“…5A), is a member of the DeuSINE superfamily (Nishihara et al, 2006), and the central sequences of ancient MIRs, a member of the CORE-SINE superfamily, were a source of binding sites for multiple transcription factors ( Fig. 4B; Bourque et al, 2008;Rohrmoser et al, 2018;Nishihara, 2019). These findings suggest the possibility that the central sequences of the SINE superfamily members have provided functional source sequences to the genome through retrotransposition and thus may have been frequently exapted in other animals.…”

CTCF As an Example of DNA-Binding Transcription Factors Containing Clusters of C2H2-Type Zinc Fingers

“…Приблизительно половина генома млекопитающих насыщена разными вариантами повторяющихся последовательностей различной природы, включая мобильные элементы и ретровирусы [129]. Большая часть изученных С2Н2-белков, и в том числе СTCF, имеют сайты связывания в мобильных элементах [130][131][132][133]. При этом такие повторяющиеся последо-вательности становятся частью регуляторных систем генов и границ ТАДов [134], что значительно расширяет возможности тонкой адаптации экспрессии генов в процессе эволюции.…”

“…Сайты связывания белков ZNF202 [126,144], ZNF263 [145], MZF1 [146], ZNF768 [133], PRDM5 [147] преимущественно найдены в промоторных областях генов, что свидетельствует о возможной роли данных факторов в активации и репрессии транскрипции.…”

“…На N-конце белка ZNF768 (рис. 1) находятся 15 гептадных повторов, имеющих сходство с C-концевым доменом РНК-полимеразы II [133] и, предположительно, участвующих в рекрутировании на промотор комплекса элонгации транскрипции.…”

The transcriptional trajectories of pluripotency and differentiation comprise genes with antithetical architecture and repetitive-element content

“…The example of MIR elements involved in enhancer and insulator function suggests that repetitive elements could be driving transcription factor binding patterns during development [ 77 ]. Indeed, Rohrmoser et al [ 78 ] used normal hematopoietic and cancer cell lines to show that ZNF768 binds to MIR elements and interacts with nuclear factors regulating gene expression.…”