# FGA, a new target of histone acetylation, inhibits apoptosis of granulosa cells in follicles

## TL;DR

FGA, a protein involved in histone acetylation, helps protect granulosa cells from apoptosis and supports follicular development in mammals.

## Contribution

FGA is identified as a novel target of histone acetylation in regulating granulosa cell survival and follicular development.

## Key findings

- FGA promotes granulosa cell proliferation and cycle progression by upregulating PCNA and CCNE1.
- FGA inhibits apoptosis by suppressing Caspase3 and Caspase9 expression in granulosa cells.
- Knockdown of HDAC2 reduces FGA transcription and chromatin accessibility at its promoter.

## Abstract

Granulosa cells (GCs) are the main supporting cells for follicles, and histone acetylation has been reported to regulate follicular development. However, the mechanism of histone acetylation regulating follicular development is still unclear in GCs. In this study, we found that FGA, fibrinogen alpha chain, mediated the survival and fate of GCs. Knockdowns of HDAC1 and HDAC3 significantly inhibited the mRNA level of FGA, while knockdown of HDAC2 notably decreased the protein level of FGA. Moreover, knockdown of HDAC2 repressed the chromatin accessibility and the enrichment level of H3K9ac at -1350/-1454 bp of FGA. In addition, FGA promoted GCs proliferation and cycle progression by up-regulating the expressions of PCNA and CCNE1, whereas it inhibited apoptosis by suppressing the expression of Caspase3. In vitro, FGA was likely to promote follicular development of pigs. In mice, FGA inhibited the apoptosis of GCs and increased the number of corpora lutea, as a result, elevating estradiol levels and advancing the day of pubertal initiation. Both in vitro and in vivo experiments, FGA promoted follicular development by up-regulating PCNA and CCNE1, while inhibited follicular apoptosis by down-regulating Caspase3 and Caspase9. Overall, knockdown of HDAC2 repressed transcription by reducing chromatin accessibility and decreasing H3K9ac binding at the FGA promoter. FGA inhibited apoptosis of GCs by suppressing the expression of Caspase3 and promoted follicular development. This study showed that FGA is a novel target for histone acetylation to regulate follicular development in mammals.