tailieunhanh - Báo cáo khoa học: Mixed lineage leukemia: roles in gene expression, hormone signaling and mRNA processing

Mixed lineage leukemias(MLLs) are an evolutionarily conserved trithorax family of human genes that play critical roles in HOXgene regulation and embryonic well known to be rearranged in myeloid and lymphoid leukemias in children and adults. There are several MLL family proteins such as MLL1, MLL2, MLL3, MLL4, MLL5, Set1A and Set1B, and each possesses histone H3 lysine 4 (H3K4)-specific methyltrans-ferase activity and has critical roles in gene activation and epigenetics. | MINIREVIEW Mixed lineage leukemia roles in gene expression hormone signaling and mRNA processing Khairul I. Ansari and Subhrangsu S. Mandal Department of Chemistry and Biochemistry The University of Texas at Arlington TX USA Keywords epigenetics estrogen receptor gene expression histone methyltransferase hormone signaling mixed lineage leukemia mRNA processing NR-box nuclear receptor SET domain Correspondence S. S. Mandal Gene Regulation and Disease Research Laboratory Department of Chemistry and Biochemistry The University of Texas at Arlington Arlington TX 76019 USA Fax 1 817 272 3808 Tel 1 817 272 3804 E-mail smandal@ Received 14 November 2009 revised 16 January 2010 accepted 28 January 2010 doi Mixed lineage leukemias MLLs are an evolutionarily conserved trithorax family of human genes that play critical roles in HOX gene regulation and embryonic development. MLL1 is well known to be rearranged in myeloid and lymphoid leukemias in children and adults. There are several MLL family proteins such as MLL1 MLL2 MLL3 MLL4 MLL5 Set1A and Set1B and each possesses histone H3 lysine 4 H3K4 -specific methyltransferase activity and has critical roles in gene activation and epigenetics. Although MLLs are recognized as major regulators of gene activation their mechanism of action target genes and the distinct functions of different MLLs remain elusive. Recent studies demonstrate that besides H3K4 methylation and HOX gene regulation MLLs have much wider roles in gene activation and regulate diverse other genes. Interestingly several MLLs interact with nuclear receptors and have critical roles in steroid-hormone-mediated gene activation and signaling. In this minireview we summarize recent advances in understanding the roles of MLLs in gene regulation and hormone signaling and highlight their potential roles in mRNA processing. Introduction In eukaryotes gene regulation is a complex process 1 . In addition to RNA polymerase II RNAPII .