Roleofrheumatoidarthritis-relatedproteinPAD4inhematopoiesis

肽精氨酸脱亚胺酶4 （PAD4）通过催化组蛋白H3精氨酸残基转化为瓜氨酸残基而发挥转录共调节作用。尽管骨髓细胞中PAD4的高水平表达表明其参与造血，但其确切作用尚不清楚。本研究显示，与其他祖细胞相比，PAD4在小鼠骨髓谱系- Sca1+ c-kit （LSK）细胞中高表达，通过催化启动子上组蛋白H3的瓜氨酸化来控制c-myc的表达。此外，PAD4与c-myc基因上游区域的淋巴细胞增强结合因子1和组蛋白去乙酰化酶1相关。与野生型小鼠相比，pad4缺陷小鼠中的LSK细胞，特别是多能祖细胞（mpp），以细胞自主方式增殖增加，这支持了这些发现。总之，我们的研究结果强烈表明，PAD4通过控制c-myc的表达来调节骨髓中mpp的增殖。

Peptidylarginine deiminase 4 (PAD4) functions as a transcriptional co-regulator bycatalyzing the conversion of histone H3 arginine residues to citrulline residues. Although the high level of PAD4 expression in bone marrow cells suggests itsinvolvement in hematopoiesis, its precise contribution remains unclear. Here, weshow that PAD4, which is highly expressed in lineage- Sca1+ c-kit (LSK) cells of mousebone marrow compared with other progenitor cells, controls c-myc expression bycatalyzing the citrullination of histone H3 on its promoter. Furthermore, PAD4 isassociated with lymphoid enhancer-binding factor 1 and histone deacetylase 1 at theupstream region of the c-myc gene. Supporting these findings, LSK cells, especiallymulti-potent progenitors (MPPs), in PAD4-deficient mice show increased proliferationin a cell-autonomous fashion compared with those in wild-type mice. Together, ourresults strongly suggest that PAD4 regulates the proliferation of MPPs in the bonemarrow by controlling c-myc expression.