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Pleiotropy01:33

Pleiotropy

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Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Regulation of Expression Occurs at Multiple Steps02:24

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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AUTS2-ポリコンブ複合体は,中枢神経系の遺伝子発現を活性化させます.

Zhonghua Gao1, Pedro Lee1, James M Stafford1

  • 1Howard Hughes Medical Institute, New York University Langone School of Medicine, Department of Biochemistry and Molecular Pharmacology, New York, New York 10016, USA.

Nature
|December 19, 2014
PubMed
まとめ
この要約は機械生成です。

驚くべきことに,自閉症感受性候補2 (AUTS2) は,ポリコンブ抑制複合体1 (PRC1) と提携して,遺伝子転写を抑制するのではなく活性化する. この発見は,表遺伝的調節と神経発達や疾患を結びつけている.

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科学分野:

  • エピジェネティクス エピジェネティクス
  • 神経生物学 神経生物学とは
  • 分子生物学は分子生物学である.

背景:

  • ポリコンブ抑制複合体1 (PRC1) は,遺伝子抑制として知られています.
  • 自閉症感受性候補2 (AUTS2) は神経疾患に関与しているが,そのメカニズムは不明である.
  • AUTS2は,自然に発生するPRC1.1の変異種に含まれています.

研究 の 目的:

  • 神経発達におけるPRC1複合体 (PRC1-AUTS2) 内のAUTS2の役割を調査する.
  • PRC1-AUTS2が遺伝子転写に影響を与えるメカニズムを解明する.

主な方法:

  • PRC1-AUTS2複合体の活性分析のための生化学研究.
  • クロマチン免疫プレシピテーションに続いて,AUTS2のゲノム標的を特定するためにシーケンシング (ChIP-seq) を行います.
  • マウスモデルにおけるAuts2の条件付きターゲティング.

主要な成果:

  • PRC1-AUTS2複合体は,正規のPRC1機能とは異なり,転写を活性化します.
  • CK2はPRC1の抑圧的活動を中和し,AUTS2はP300を遺伝子活性化のために採用する.
  • AUTS2は,プロモーターアソシエーションを通じて神経細胞の遺伝子発現を調節する.
  • マウスのCNSにおける条件付きAuts2の削除は,発達障害を引き起こす.

結論:

  • AUTS2はPRC1の活動を破壊し,それを抑圧から活性化へとシフトさせます.
  • このメカニズムは,PRC1-AUTS2による表遺伝子調節と神経細胞の遺伝子発現と発達を結びつける.
  • 発見は,AUTS2障害に関連した神経疾患の病原性についての洞察を提供します.