Dr. Walsh, along with Dr. Ming-Ming Zhou, is investigating the regulation of the Polycomb group (PcG) and Trithorax (Trx) protein complexes in exerting gene control through the mechanism of binding between long non-coding RNAs, methyllysine and mono-ubiquitinated lysine residues in nucleosomal histones during early embryonic development and in oncogenesis. Dr. Walsh has recently directed an effort to understand the role of long non-coding RNAs (ncRNAs) to mediate the function of Polycomb Repressive Complexes (PRCs) 1 and 2. Transcription is pervasive throughout the mammalian genome, however, many RNA transcripts lack coding seuqences in the genome but have been shown to impose an architectural function in chromatin. Recent studies have also shown that long ncRNAs are an instructional component of chromatin that mediates the function of PRC1 and PRC2 to further impose histone modifications for epigenetic gene silencing. Current studies by RNA ChIP-Seq are evaluating the role of ncRNAs that mask the human genome to coordinate PRC function during early embryonic development and in human disease.
Barradas M, Anderton E, Acosta JC, Li S, Banito A, Rodriguez-Niedenfuhr M, Banck M, Zhou M-M, Walsh MJ, Peters G, Gil J. Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes Dev. 2009 May 15;23(10).
Banck MS, Li S, Nishio H, Wang C, Beutler AS, Walsh MJ. The ZNF217 oncogene is a candidate organizer of repressive histone modifiers. Epigenetics. 2009 Feb 23;4(2):1-9.
Qian C, Li S, Jakoncic J, Zeng L, Walsh MJ, Zhou MM. Structure and hemimethylated CpG binding of the SRA domain from human UHRF1. J Biol Chem. 2008 Dec 12;283(50):34490-4.
Pless O, Kowenz-Leutz E, Knoblich M, Lausen J, Beyermann M, Walsh MJ, Leutz A. G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta. J Biol Chem. 2008 Sep 26;283(39):26357-63.
Tan CC, Sindhu KV, Li S, Nishio H, Stoller JZ, Oishi K, Puttreddy S, Lee TJ, Epstein JA, Walsh MJ, Gelb BD. Transcription factor Ap2delta associates with Ash2l and ALR, a trithorax family histone methyltransferase, to activate Hoxc8 transcription. Proc Natl Acad Sci U S A. 2008 May 27;105(21):7472-7.
Marango J, Shimoyama M, Nishio H, Meyer JA, Min DJ, Sirulnik A, Martinez-Martinez Y, Chesi M, Bergsagel PL, Zhou MM, Waxman S, Leibovitch BA, Walsh MJ, Licht JD. The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor. Blood. 2008 Mar 15;111(6):3145-54.
Paul T, Li S, Khurana S, Leleiko NS, Walsh MJ. The epigenetic signature of CFTR expression is co-ordinated via chromatin acetylation through a complex intronic element. Biochem J. 2007 Dec 15;408(3):317-26.