Histone chaperone ASF1B promotes humanβ-cell proliferation via recruitment of histone H3.3

Abstract

Anti-silencing function 1 (ASF1) is a histone H3-H4 chaperone involved in DNA replication and repair, and transcriptional regulation. Here, we identify ASF1B, the mammalian paralog to ASF1, as a proliferationinducing histone chaperone in human b-cells. Overexpression of ASF1B led to distinct transcriptional signatures consistent with increased cellular proliferation and reduced cellular death. Using multiple methods of monitoring proliferation and mitotic progression, we show that overexpression of ASF1B is sufficient to induce human b-cell proliferation. Co-expression of histone H3.3 further augmented b-cell proliferation, whereas suppression of endogenous H3.3 attenuated the stimulatory effect of ASF1B. Using the histone binding-deficient mutant of ASF1B (V94R), we show that histone binding to ASF1B is required for the induction of b-cell proliferation. In contrast to H3.3, overexpression of histone H3 variants H3.1 and H3.2 did not have an impact on ASF1B-mediated induction of proliferation. Our findings reveal a novel role of ASF1B in human b-cell replication and show that ASF1B and histone H3.3A synergistically stimulate human b-cell proliferation.

ASF1B promotes cervical cancer progression through stabilization of CDK9

“…ASF1 exists as two paralogs: ASF1A and ASF1B. ASF1A contributes primarily to DNA repair and cell senescence, while ASF1B is preferentially involved in cell proliferation 22,23 . Interestingly, Armelle et al revealed that a high mRNA level of ASF1B was correlated with clinical data and disease outcome in breast cancer, and the researchers proposed that ASF1B might be used as a new proliferation marker for breast cancer diagnosis and prognosis 24 .…”

Tangshen Formula Treatment for Diabetic Kidney Disease by Inhibiting Racgap1-stata5-Mediated Cell Proliferation and Restoring miR-669j-Arntl-Related Circadian Rhythm

“…It has been reported that depletion of histone H3–H4 chaperone Asf1b severely compromises proliferation, leading to aberrant nuclear structures and a distinct transcriptional signature, while its overexpression increases cellular proliferation, promoting tumor progression and predicting poor outcomes [ 25 ]. This effect of Asf1b was also observed in β cell proliferation [ 26 ]. Anln is an actin-binding protein required for cytokinesis.…”

Two Novel Candidate Genes for Insulin Secretion Identified by Comparative Genomics of Multiple Backcross Mouse Populations

“…In recent years, it has become increasingly clear that the different subunits of the ribonuclease P complex are engaged in other important roles. Pop4 has recently been shown to be involved in the DNA damage response machinery (Abu-Zhayia et al 2017), and to participate in the regulation of chromatin structure and function (Newhart et al 2016), which is known to play a fundamental role in the epigenetic modification of the genome and likely also in b-cell biology (Paul et al 2016). In humans, copy number variants of POP4 have been associated with breast and ovarian cancer (Wrzeszczynski et al 2011;Natrajan et al 2012).…”